Pulsed Radiofrequency

Number: 0735

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses pulsed radiofrequency.

  1. Experimental and Investigational

    1. Aetna considers pulsed radiofrequency experimental and investigational for all indications, including those in the following list, because its effectiveness has not been established:

      1. Abdominal cutaneous nerve entrapment syndrome
      2. Carpal tunnel syndrome
      3. Cervical radicular pain
      4. Chronic hip pain
      5. Chronic knee pain
      6. Chronic lumbosacral radicular pain
      7. Chronic pain following inguinal herniotomy
      8. Chronic perineal pain
      9. Coccydynia
      10. Diabetic peripheral neuropathy
      11. Discogenic pain
      12. Face and head pain
      13. Facet and sacroiliac joint arthropathy
      14. Frozen shoulder (adhesive capsulitis)
      15. Glossopharyngeal neuralgia
      16. Headache (including cervicogenic headache)
      17. Hemiplegic shoulder pain
      18. Idiopathic axonal polyneuropathy
      19. Idiopathic supraorbital neuralgia
      20. Infraorbital neuralgia
      21. Inguinal neuralgia
      22. Intercostal neuralgia after lung cancer surgery
      23. Intercostobrachial neuralgia in post-mastectomy pain syndrome
      24. Interstitial cystitis
      25. Low back pain
      26. Lower extremity neuralgia
      27. Lumbar herniated nucleus pulposus
      28. Lumbo-sacral radicular syndrome
      29. Meralgia paresthetica
      30. Metatarsalgia
      31. Metatarso-phalangeal joint pain
      32. Morton's neuroma
      33. Myofascial pain syndrome of gastrocnemius / the trapezius muscle
      34. Myofascial or neuromatous pain
      35. Neck pain
      36. Occipital neuralgia
      37. Ophthalmic neuralgia
      38. Orchalgia
      39. Osteoarthritis of the knee
      40. Pain associated with tumors involving peripheral nerves
      41. Palmar hyperhidrosis
      42. Pelvic pain
      43. Perineal pain
      44. Peripheral neuralgia
      45. Peripheral post-traumatic neuropathic pain
      46. Periscapular pain
      47. Post-herpetic itch
      48. Post-herpetic neuralgia
      49. Post-surgical orchialgia
      50. Plantar fasciitis
      51. Premature ejeculation
      52. Pudendal neuralgia
      53. Reflex sympathetic dystrophy/complex regional pain syndrome
      54. Sacro-iliac joint pain
      55. Sensory deficits following stroke
      56. Shoulder pain
      57. Striae rubra
      58. Stump pain
      59. Sural neuralgia
      60. Tarsal tunnel syndrome
      61. Testicular pain (orchialgia)
      62. Thoracic pain
      63. Tinnitus
      64. Trapezio-metacarpal joint pain
      65. Trigeminal neuralgia
      66. Urinary urgency and hesitancy
      67. Vaginismus
      68. Ventricular arrhythmias (fibrillation or tachycardia)
      69. Vulvodynia
      70. Zoster-related pain
      71. Zygapophyseal joint pain;

    2. Aetna considers the the following pulsed radiofrequency modalities experimental and investigational because its effectiveness has not been established:

      1. Stimpod NMS460 nerve stimulator (Xavant Technology)
      2. Wearable pulsed radiofrequency therapy device for treatment of post-amputation pain.

  2. Related Policies

    1. CPB 0016 - Back Pain - Invasive Procedures for conventional radiofrequency facet denervation
Table:

CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

There are no specific codes for pulsed radiofrequency:

HCPCS codes not covered for indications listed in the CPB:

Stimpod NMS460 nerve stimulator (Xavant Technology) - no specific code:

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
B02.21 - B02.29 Zoster with other nervous system involvement [post-herpetic neuralgia]
D21.0 - D21.9 Other benign neoplasms of connective and other soft tissue [neuromatous pain]
D36.10 - D36.17 Benign neoplasm of peripheral nerves and automatic nervous system [neuromatous pain]
E08.40 - E08.49 Diabetes mellitus due to underlying condition with neurological complications
E09.40 - E09.49 Drug or chemical induced diabetes mellitus with neurological complications
E10.40 - E10.49 Type 1 diabetes mellitus with neurological complications
E11.40 - E11.49 Type 2 diabetes mellitus with neurological complications
E13.40 - E13.49 Other specified diabetes mellitus with neurological complications
F52.4 Premature ejaculation
G09.01 - G09.09 Idiopathic peripheral autonomic neuropathy [peripheral neuralgia]
G44.1 Vascular headache, not elsewhere classified
G50.0 Trigeminal neuralgia
G52.1 Disorders of glossopharyngeal nerve
G56.00 - G56.03 Carpal tunnel syndrome
G57.0 - G57.93 Mononeuropathies of lower limb [pudendal nerve entrapment or neuropathy] [lower extremity neuralgia] [tarsal tunnel syndrome] [sural neuralgia]
G58.0 Intercostal neuropathy [intercostobrachial neuralgia in post mastectomy pain syndrome]
G58.8 - G58.9 Other specified and unspecified mononeuropathy [pudendal nerve entrapment or neuropathy]
G60.3 Idiopathic progressive neuropathy [idiopathic axonal polyneuropathy]
G60.8 - G60.9 Other and unspecified hereditary and idiopathic neuropathies [idiopathic axonal polyneuropathy]
G81.0 - G81.94 Hemiplegia and hemiparesis
G89.21 - G89.28 Chronic pain, not elsewhere classified
G89.3 Neoplasm related pain (acute) (chronic) [tumors involving peripheral nerves]
G90.50 - G90.59 Complex regional pain syndrome I (CRPSI)
H93.11 – H93.19 Tinnitus
I47.0 Re-entry ventricular arrhythmia
I47.20, I47.21, I47.29 Ventricular tachycardia
I49.01 Ventricular fibrillation
I69.398 Other sequelae of cerebral infarction
L74.510 - L74.9 Focal hyperhidrosis [palmar hyperhidrosis]
L90.6 Striae atrophicae [striae rubra]
M12.9 Arthropathy, unspecified [facet and sacroiliac joint]
M17.0 - M17.9 Osteoarthritis of knee
M25.50 - M25.579 Pain in joint [zygapophyseal] [metatarso-phalangeal] [trapezio-metacarpal]
M51.15 - M51.17 Thoracolumbar and lumbosacral intervertebral disc disorders with radiculopathy
M51.26 Other intervertebral disc displacement, lumbar region
M51.9 Unspecified thoracic, thoracolumbar and lumbosacral intervertebral disc disorder [discogenic pain]
M53.3 Sacrococcygeal disorders, not elsewhere classified [sacroiliac joint pain]
M54.10 Radiculopathy, site unspecified [pudendal]
M54.12 Radiculopathy, cervical region
M54.17 Radiculopathy, lumbosacral region
M54.18 Radiculopathy, sacral and sacrococcygeal region [pudendal]
M54.2 Cervicalgia
M54.50 - M54.59 Low back pain [lumbago]
M54.6 Pain in thoracic spine
M54.81 Occipital neuralgia
M54.89 - M54.9 Other and unspecified dorsalgia
M72.2 Plantar fascial fibromatosis
M75.00 - M75.02 Adhesive capsulitis of shoulder
M77.40 - M77.42 Metatarsalgia
M79.10 - M78.18 Myalgia [myofascial pain]
M79.2 Neuralgia and neuritis, unspecified [pudendal] [[idiopathic supraorbital neuralgia] [peripheral post-traumatic neuropathic pain] [infraorbital neuralgia]
M79.601 - M79.676 Pain in limp, hand, foot, fingers and toes [stump pain]
N50.811 - N50.819 Testicular pain
N94.2 Striae atrophicae [striae rubra]
N94.810 - N94.819 Vulvodynia
R10.2 Pelvic and perineal pain
R39.11 Hesitancy of micturition
R39.15 Urgency of urination
R51 Headache
R52 Pain, unspecified [chronic pain NOS]
Z89.01 - Z89.9 Acquired absence of limb [stump pain]

Background

Radiofrequency (RF) treatment is a minimally invasive procedure that has been used for over three decades in treating various chronic pain syndromes such as trigeminal neuralgia, post-herpetic neuralgia, low back pain (LBP), and complex regional pain syndrome/reflex sympathetic dystrophy.  It is a palliative treatment not without complications.  Radiofrequency procedures have been reported to be associated with high number of complications compared with other ablative neurosurgical techniques.  Furthermore, conventional (continuous) RF treatment occasionally results in worsening and even new onset of pain. 

The use of pulsed radiofrequency (PRF, also known as cold RF), a non- or minimally-neurodestructive and thus less painful technique, serves as an alternative to conventional RF therapy.  Pulsed radiofrequency treatment, performed under fluoroscopic guidance, entails the use of pulsed time cycle that delivers short bursts of RF energy to nervous tissue. Pulsed radiofrequency is a proposed alternative to traditional radiofrequency neurotomy. Pulsed radiofrequency delivers short bursts of radiofrequency current instead of a continuous flow, which allows the needle to remain relatively cool so that the tissue cools slightly between each burst, reducing the risk of destroying nearby tissue. 

The available evidence on the effectiveness of PRF in the treatment of patients with various chronic pain syndromes is largely based on retrospective, case series studies.  Its clinical value needs to be examined in well-designed, randomized controlled trials with large sample size and long-term follow-up.

In a case series study, Mikeladze and colleagues (2003) reported that application of PRF to medial branches of the dorsal rami in patients with chronic facet joint arthropathy provided temporary pain relief in 57.6 % (68 of 118) of patients.  The procedure was successful and lasted on average 3.93 +/- 1.86 months.

Pevzner and co-workers (2005) reported the findings in 28 patients (LBP = 20, cervical pain = 8; average age of 56.7 years) who were treated by PRF and followed for 3, 6 and 12 months.  The 3-month follow-up revealed the following results: excellent results in 2 cases (7.1 %), good results in 12 cases (42.9 %), fair in 9 (32.1 %), and 5 (17.9 %) reported that their condition have not changed.  Results after 6 and 12 months were excellent in 2 (both groups), good in 7 and 6 respectively, 11 fair (both groups), and unresponsive to treatment was noticed in 8 patients after 6 and 9 patients after 12 months.  Significant reduction was found in the visual analog scale (VAS) for pain from an average of 8.8 to 4.2 after 3 months, 4.8 after 6 months and 4.9 after 1 year.  The authors concluded that PRF is a safe and simple procedure to control radicular pain in the lumbar and cervical regions.  Moreover, they emphasized the need for further prospective, double-blind studies to better ascertain the clinical value of this technique.

Bayer and associates (2005) evaluated the effectiveness of spheno-palatine ganglion PRF (SPG-PRF) treatment in patients suffering from chronic head and face pain.  A total of 30 patients were observed from 4 to 52 months after PRF treatment.  The primary outcome measures were reduction in oral medication use (including opioids), time to next treatment modality for presenting symptoms, duration of pain relief, and the presence of residual symptoms.  Secondary outcome measures included the evaluation of adverse effects and complications.  All data were derived from patient charts, phone conversations, and clinical follow-up visits. A total of 14 % of respondents reported no pain relief, 21 % had complete pain relief, and 65 % of the patients reported mild-to-moderate pain relief from SPG-PRF treatment.  A total of 65 % of the respondents reported mild-to-moderate reduction in oral opioids.  None of the patients developed significant infection, bleeding, hematoma formation, dysesthesia, or numbness of palate, maxilla, or posterior pharynx.  The authors concluded that these findings suggested that a prospective, randomized, controlled study to confirm the safety and effectiveness of PRF treatment for chronic head and face pain is justified.

Vallejo and co-workers (2006) presented a prospective case series on the treatment of intractable sacroiliac joint (SIJ) dysfunction with PRF denervation (PRFD) of lateral branches from L4 to S3.  A total of 126 patients with presumptive SIJ dysfunction based on history and physical examination underwent arthrographically confirmed steroid/local anesthetic SIJ injection.  Fifty-two patients (41.3 %) had greater than 75 % pain relief after 2 consecutive injections, physical therapy, repeated SIJ injections, and/or analgesics.  A total of 22 patients failed to respond; these individuals underwent PRFD of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2.  Visual analog score and quality of life (QOL) assessments were performed before and after treatment.  Sixteen patients (72.7 %) experienced "good" (greater than 50 % reduction in VAS), or "excellent" (greater than 80 % reduction in VAS) pain relief following PRFD.  Duration of pain relief ranged from 6 to 9 weeks in 4 patients, 10 to 16 weeks in 5 patients, and 17 to 32 weeks in 7 patients.  In addition, QOL scores improved significantly in all measured categories.  Six patients (26.1 %) did not respond to PRFD and had less than 50 % reduction in VAS and were considered failures.  The authors concluded that PRFD of the lateral branch of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2 is an effective treatment for some patients with SIJ pain unresponsive to other forms of therapy.

Teixeira and Sluijter (2006) stated that intra-discal RF, with the electrode placed in the center of the nucleus pulposus, has been a controversial procedure in patients with discogenic pain.  These researchers examined the effect of high-voltage, long-duration intra-discal PRF in patients with 1-level discogenic LBP (n = 8), as confirmed by discography.  The pain intensity score on a 0 to 10 Numeric Rating Scale (NRS) was used as outcome measure.  The mean duration of pain was 6.3 years (range of 0.5 to 16 years, median of 4 years).  The mean NRS score was 7.75 (range of 5 to 9).  Disc height was reduced 60 % in 1 patient and up to 30 % in the remaining subjects.  A 15-cm, 20-G needle with a 15-mm active tip was placed centrally in the disc.  Pulsed radiofrequency was applied for 20 mins at a setting of 2 x 20 ms/s and 60 V.  There was a very significant drop in the NRS scores over the first 3 months (p < 0.0001).  On an individual basis, all patients had a fall of the NRS score of at least 4 points at the 3-month follow-up.  A follow-up of 12.8 months (range of 6 to 25 months, median of 9 months) was available for 5 patients.  All these patients are now pain-free, except for 1 patient with an NRS score of 2.  The authors concluded that this method merits a controlled, prospective study.

Lindner et al (2006) noted that the use of PRF for the treatment of lumbar medial branch for facet pain is controversial.  These investigators reported the findings of a retrospective study of PRF treatment of the medial branch in 48 patients with chronic LBP.  Patients who did not respond were offered treatment with conventional RF heat lesions.  Patients with LBP and greater than 50 % pain relief following a diagnostic medial branch block were included in the study.  The mean age was 53.1 +/- 13.5 years; the mean duration of pain was 11.4 +/- 10.9 years.  Nineteen patients had undergone surgery.  Pain scores on a NRS of 1 to 10 were noted before and after the diagnostic nerve block, before the procedure, and at 1-month and 4-month follow-up.  PRF was applied for 2 mins at a setting of 2 x 20 ms/s and 45 V at a minimum of 2 levels using a 22-G electrode with a 5-mm active tip.  Heat lesions were made at 80 degrees Centigrade (C) for 1 min.  A successful outcome was defined as a greater than 60 % improvement on the NRS at 4-month follow-up.  In 21/29 non-operated patients and 5/19 operated patients, the outcome was successful.  In the unsuccessful patients who were subsequently treated with heat lesions, the success rate was 1/6.  The authors concluded that the setup of the study did not allow a comparison with the results of conventional/continuous RF (CRF) for the same procedure, other than the detection of an obvious trend.  When comparing these findings with various studies on CRF of the medial branch such a trend could not be found.  Based on these retrospective data, prospective and randomized studies (e.g., PRF versus CRF) are justified.

In the only prospective, randomized, double-blinded, controlled trial of PRF for trigeminal neuralgia published to date, Erdine and colleagues (2007) compared PRF to CRF in the treatment of idiopathic trigeminal neuralgia.  A total of 40 patients were randomly assigned to PRF or CRF.  Visual analog scale scores decreased significantly (p < 0.001) and patient satisfaction scale (PSS) scores improved significantly (p < 0.001) after the procedure in subjects assigned to CRF.  The VAS score decreased in only 2 of 20 patients from the PRF group and pain recurred 3 months following the procedure.  At the end of 3 months, CRF was performed in patients assigned to PRF because all patients in this group still exhibited intractable pain.  The authors concluded that PRF is ineffective in treating trigeminal neuralgia.

In a Cochrane review, Zakrzewska and Akram (2011) evaluated the efficacy of neurosurgical interventions for classical trigeminal neuralgia in terms of pain relief, quality of life and any harms, and determined if there are defined subgroups of patients more likely to benefit.  These investigators searched the Cochrane Neuromuscular Disease Group Specialized Register, (May 13, 2010), CENTRAL (issue 2, 2010 part of the Cochrane Library), Health Technology Assessment (HTA) Database, NHS Economic Evaluation Database (NHSEED) and Database of Abstracts of Reviews of Effects (DARE) (issue 4, 2010 (HTA, NHSEED and DARE are part of the Cochrane Library)), MEDLINE (January 1966 to May 2010) and EMBASE (January 1980 to May 2010) with no language exclusion.  Randomized controlled trials (RCTs) and quasi-RCTs of neurosurgical interventions used in the treatment of classical trigeminal neuralgia were selected for analysis.  Two authors independently assessed trial quality and extracted data.  They contacted authors for clarification and missing information whenever possible.  A total of 11 studies involving 496 participants met some of the inclusion criteria stated in the protocol.  One hundred and eighty patients in 5 studies had peripheral interventions, 229 patients in 5 studies had percutaneous interventions applied to the Gasserian ganglion, and 87 patients in 1 study underwent 2 modalities of stereotactic radiosurgery (Gamma Knife) treatment.  No studies addressing microvascular decompression (which is the only non-ablative procedure) met the inclusion criteria.  All but 2 of the identified studies had a high-to-medium risk of bias because of either missing data or methodological inconsistency.  It was not possible to undertake meta-analysis because of differences in the intervention modalities and variable outcome measures.  Three studies had sufficient outcome data for analysis.  One trial, which involved 40 participants, compared 2 techniques of RF thermocoagulation (RFT) of the Gasserian ganglion at 6 months.  Pulsed RFT resulted in return of pain in all participants by 3 months.  When this group were converted to conventional (continuous) treatment these participants achieved pain control comparable to the group that had received conventional treatment from the outset.  Sensory changes were common in the continuous treatment group.  In another trial, of 87 participants, investigators compared radiation treatment to the trigeminal nerve at 1 or 2 isocenters in the posterior fossa.  There were insufficient data to determine if one technique was superior to another.  Two isocenters increased the incidence of sensory loss.  Increased age and prior surgery were predictors for poorer pain relief.  Relapses were non-significantly reduced with 2 isocenters (risk ratio (RR) 0.72, 95 % confidence intervaI (CI): 0.30 to 1.71).  A 3rd study compared 2 techniques for RFT in 54 participants for 10 to 54 months.  Both techniques produced pain relief (not significantly in favor of neuronavigation (RR 0.70, 95 % CI: 0.46 to 1.04) but relief was more sustained and side effects fewer if a neuronavigation system was used.  The remaining 8 studies did not report outcomes as pre-determined in the protocol.  The authors concluded that there is very low quality evidence for the efficacy of most neurosurgical procedures for trigeminal neuralgia because of the poor quality of the trials.  All procedures produced variable pain relief, but many resulted in sensory side effects.  There were no studies of microvascular decompression which observational data suggested gives the longest pain relief.  There is little evidence to help comparative decision making about the best surgical procedure.  They stated that well-designed studies are urgently needed.

In a case series study, Martin and colleagues (2007) reported the effectiveness of PRF in the treatment of patients with lumbosacral spondylosis.  This case series reviewed 22 patients who had been previously treated with PRF with good results.  Patients who had been prescribed opioids were excluded from this study.  During the PRF application, tissue temperature was limited to 43 degrees C.  A minimum of 200 mA of current was delivered in each case.  The minimum current (at 50 Hz) necessary to stimulate the involved nerve was recorded.  The time from PRF treatment until the patient requested a subsequent application was documented.  The effective duration of PRF in patients treated for lumbosacral spondylosis ranged from 5 to 18 months (mean +/- standard deviation [SD]: 9 +/- 3.7 months; n = 16).  Administrations of PRF to dorsal root ganglion (DRG) were effective from 2 to 12 months (7 +/- 3.8 months; n = 8).  Similar results were observed when PRF was applied to cervical medial branch nerves, one suprascapular nerve, and one stellate ganglion.  The mean sensory stimulation thresholds obtained before treatment ranged from 0.08 V to 0.14 V.  The authors concluded that in this select population of patients who did not receive opioids, and had a favorable response to a previous PRF application, the duration of pain relief supported the use of PRF as an effective pain treatment.

In a retrospective study, Abejon and associates (2007) assessed the effectiveness of PRF applied to the lumbar DRG for the treatment of LBP.  This study analyzed the findings of 54 patients who underwent 75 PRF procedures.  Patients were divided into 3 groups according to the etiology of the lesion
  1. herniated disc (HD),
  2. spinal stenosis (SS), and
  3. failed back surgery syndrome (FBSS). 
The analgesic effectiveness of the technique was assessed using a 10-point NRS at baseline and, along with the Global Perceived Effect (GPE), at 30, 60, 90, and 180 days.  The reduction in pain medications and the number of complications associated with the technique were assessed.  A decrease in the NRS score was observed in patients with HD (p < 0.05) and SS (p < 0.001), but not in those with FBSS.  The GPE scores confirmed this finding.  No complications were noted.  The authors concluded that PRF of the DRG was significantly more effective in HD and SS than in FBSS patients.  The application of PRF was ineffective in FBSS.

Van Zundert and associates (2007) examined the effect of PRF for the treatment of patients with chronic cervical radicular pain.  A total of 23 patients, out of 256 screened, met the inclusion criteria and were randomly assigned in a double-blind fashion to receive either PRF or sham intervention.  The evaluation was carried out by an independent observer.  At 3-month follow-up, the PRF group showed a significantly better outcome with regard to the global perceived effect (i.e., greater than 50 % improvement) and VAS (i.e., 20 point pain reduction).  The quality of life scales also showed a positive trend in favor of the PRF group, but significance was only reached in theShort Form-36 questionnaire (SF-36) domain vitality at 3 months.  The need for pain medication was significantly reduced in the PRF group after 6 months.  No complications were observed during the study period.  These findings are in agreement with the results of the authors' previous clinical audit that PRF treatment of the cervical DRG may provide pain relief for a limited number of carefully selected patients with chronic cervical radicular pain as assessed by clinical and neurological examination.

In an editorial that accompanied the study by Van Zundert et al, Jensen (2007) noted that early studies show good short-term results of PRF.  However, there is currently insufficient evidence to use PRF routinely for chronic cervical radicular pain.  Jensen stated that more research is needed to ascertain the best way to use PRF and its analgesic mechanism.  This is in agreement with the observation of Tella and Stojanovic (2007) who stated that more studies are needed to support the routine use of PRF for treating patients with chronic cervical radicular pain.

Cahana and associates (2006) stated that the clinical advantages and mechanisms of PRF remain unclear.  These investigators reviewed clinical and laboratory data on PRF.  The final analysis yielded 58 reports on the clinical use of PRF in different applications: 33 full publications and 25 abstracts.  They also retrieved 6 basic science reports, 5 full publications, and 1 abstract.  The authors stated that the accumulation of these data showed that the use of PRF generates an increasing interest of pain physicians for the management of a variety of pain syndromes.  Although the mechanism of action has not been fully elucidated, laboratory reports suggested a neurobiological phenomenon altering the pain signaling, which some researchers have described as neuromodulatory.  No side effects related to PRF were reported to date.  The authors concluded that further research in the clinical and biological effects of this technique is justified.

In a review on PRF treatment, Gallagher (2006) stated that "we should cautiously prescribe this promising intervention following clinical algorithms that are based upon the best clinical evidence available.  However, it is critically important to avoid the mistake of creating a "carte blanche" environment for those practitioners who would abuse the privilege and opportunity presented by this new technology, besmirching our credibility and ultimately impeding the opportunity to use this treatment to the benefit of the public.  Ultimately, evidence, not reimbursement, should determine whether pulsed radiofrequency finds a place in our clinical toolbox".

It should be noted that the Reflex Sympathetic Dystrophy Syndrome Association (2006) did not recommend PRF for the treatment of patients with complex regional pain syndrome.  It stated that future studies may expand on the role of PRF techniques or such unstudied techniques as cryosurgery as alternative therapies to treat patients with sympathetically maintained pain.  The Transport Accident Commission, a government-owned organization of the State of Victoria in Melbourne, Australia (2007) does not consider PRF neurotomy/denervation as part of spinal injection therapy.

Malik and Benzon (2007) reviewed the available literature on PRF and determined its clinical efficacy. Their search of the literature yielded 341 citations; and 51 relevant articles were found.  There were 4 review articles: 44 articles pertained to the application of PRF by an electrode placed in the vicinity of a neural structure.  Of these, only 2 were randomized controlled trials (RCTs).  Of the remaining 42 articles, 1 was a non-RCT, 3 were prospective uncontrolled trials: there were 6 retrospective studies, 11 case reports, 8 laboratory studies, 2 position papers, 5 editorials and 7 items of correspondence, while 1 publication reported 2 studies.  Three articles pertained to transcutaneous application of PRF.  Of the 2 RCTs, 1 reported efficacy of the PRF while the other reported it to be ineffective.  The majority of the uncontrolled and observational studies reported clinical efficacy of PRF, however many of these studies had limitations.  The authors concluded that further RCTs are needed for pain physicians to clearly understand the role of PRF in the treatment of various chronic pain syndromes.  Furthermore, these investigators (Malik and Benzon, 2008) stated that larger RCTs are needed to
  1. assess the long-term effects of RF applications (pulsed and continuous mode) to dorsal root ganglia and
  2. determine the precise mode of action of this trechnique.

Simopoulos and colleagues (2008) prospectively evaluated the response and safety of pulsed and continuous RF lesioning of the dorsal root ganglion/segmental nerves in patients with chronic lumbosacral radicular pain.  A total of 76 patients with chronic lumbosacral radicular pain refractory to conventional therapy met the inclusion criteria and were randomly assigned to 1 of 2 types of treatment, PRF lesioning of the dorsal root ganglion/segmental nerve or PRF followed immediately by continuous RF.  Patients were carefully evaluated for neurological deficits and side effects.  The response was evaluated at 2 months and was then tracked monthly.  A Kaplan-Meier analysis was used to illustrate the probability of success over time and a Box-Whisker analysis was applied to determine the mean duration of a successful analgesic effect.  Two months after undergoing RF treatment, 70 % of the patients treated with PRF and 82 % treated with pulsed and continuous RF had a successful reduction in pain intensity.  The average duration of successful analgesic response was 3.18 months (+/- 2.81) in the group treated with PRF and 4.39 months (+/- 3.50) in those patients treated with pulsed and continuous RF lesioning.  A Kaplan-Meier analysis illustrated that in both treatment groups the chance of success approached 50 % in each group at 3 months.  The vast majority of patients had lost any beneficial effects by 8 months.  There was no statistical difference between the 2 treatment groups. No side effects or neurological deficits were found in either group.  The authors concluded that pulsed mode RF of the dorsal root ganglion of segmental nerves appears to be a safe treatment for chronic lumbosacral radicular pain.  A significant number of patients can derive at least a short-term benefit.  The addition of heat via continuous radiofrequency does not offer a significant advantage.  A RCT trial is now required to ascertain the effectiveness of PRF.

Byrd and Mackey (2008) stated that the mechanism by which PRF controls pain is unclear, but it may involve a temperature-independent pathway mediated by a rapidly changing electrical field.  Although much anecdotal evidence exists in favor of PRF, there are few quality studies substantiating its utility.

In a pilot study, Misra et al (2009) evaluated the effectiveness of PRF of spermatic cord in the treatment of chronic testicular pain.  A total of 10 patients with chronic testicular pain were treated with PRF stimulation of the spermatic cord.  A RF probe placed percutaneously into the spermatic cord was used to deliver four 120-second cycles of 20-millisecond pulses at 2 Hz.  Test stimulation was first used to confirm the precise placement of the probe.  The short-form McGill Pain Questionnaire was used to assess pain before treatment and at 3 months.  Patients who had experienced improvement were followed-up by telephone, to determine if pain relief was sustained.  Ten patients were entered into the study but 1 was lost to follow-up.  Of the 9 patients evaluated, 4 had complete resolution of pain, while 1 had partial pain relief.  Three patients experienced no change and 1 reported that his pain was worse.  All patients who experienced complete and partial pain relief continued to do so at a mean long-term follow-up of 9.6 months (range of 3 to 14 months).  There were no complications observed immediately or during the follow-up period.  The authors reported that pain scores improved in 5 out of 9 patients.  They concluded that PRF of spermatic cord appears to be a safe minimally invasive outpatient procedure that should be investigated further with placebo-controlled trials.

In a case series study, Tamimi and colleagues (2009) examined the use of PRF in the treatment of myofascial trigger points and scar neuromas.  A total of 9 patients were treated over an 18-month period.  All patients had longstanding myofascial or neuromatous pain that was refractory to previous medical management, physical therapy, and trigger point injections.  Eight out of 9 patients experienced 75 to 100 % reduction in their pain following PRF treatment at initial evaluation 4 weeks following treatment.  Six out of 9 (67 %) patients experienced 6 months to greater than 1 year of pain relief.  One patient experienced no better relief in terms of degree of pain reduction or duration of benefit when compared with previous trigger point injections.  No complications were noted.  The authors stated that these findings suggested that PRF could be a minimally invasive, less neurodestructive treatment modality for these painful conditions and that further systematic evaluation of this treatment approach is needed.

Basal et al (2010) noted that premature ejaculation (PE) is the most common sexual problem experienced by men, and affecting 20 to 30 % of them.  Pulsed radiofrequency neuromodulation has been stuided as a treatment for various pain conditions.  These researchers used PRF to treat PE by desensitizing dorsal penile nerves in patients resistant to conventional treatments.  A total of 15 patients with a lifelong history of PE, defined as an intra-vaginal ejaculatory latency time (IELT) of less than 1 min that occurred in more than 90 % of intercourses and resistant to conventional treatments, were enrolled in this study.  Patients with erectile dysfunction were excluded.  The mean age of the patients was 39 +/- 9 years.  Before and 3 weeks after the treatment, IELT and sexual satisfaction scores (SSS) (for patients and their partners) were obtained.  The mean IELT before and 3 weeks after procedure were 18.5 +/- 17.9 and 139.9 +/- 55.1 seconds, respectively.  There were no side effects.  Mean SSS of patients before and after treatment were 1.3 +/- 0.3 and 4.6 +/- 0.5 and mean SSS of partners before and after treatment were 1.3 +/- 0.4 and 4.4 +/- 0.5, respectively.  In all cases, IELT and SSS were significantly increased (p < 0.05).  None of the patients and their wives defined any treatment failure during the follow-up period.  The mean follow-up time was 8.3 +/- 1.9 months.  The authors stated that it is early to conclude that this new treatment modality might be used widely for the treatment of PE, however being an innovative modality, placebo controlled studies (e.g., sham procedure), with larger number of patients, including assessment of penil sensitivity (e.g., biothesiometry) are needed.

Vanelderen et al (2010) reported on the results of a prospective trial with 6 months of follow-up in which PRF treatment of the greater and/or lesser occipital nerve was used to treat occipital neuralgia.  Patients presenting with clinical findings suggestive of occipital neuralgia and a positive test block of the occipital nerves with 2 ml of local anesthetic underwent a PRF procedure of the culprit nerves.  Mean scores for pain, quality of life, and medication intake were measured 1, 2, and 6 months following the procedure.  Pain was measured by the visual analog and Likert scales, quality of life was measured by a modified brief pain questionnaire, and medication intake was measured by a Medication Quantification Scale.  During a 29-month period, 19 patients were included in the study.  Mean VAS and median Medication Quantification Scale scores declined by 3.6 units (p = 0.002) and 8 units (p = 0.006), respectively, during 6 months.  Approximately 52.6 % of patients reported a score of 6 (pain improved substantially) or higher on the Likert scale after 6 months.  No complications were reported.  The authors concluded that PRF treatment of the greater and/or lesser occipital nerve is a promising treatment of occipital neuralgia.  They stated that this study warrants further placebo-controlled trials.

Choi et al (2012) reported the results of PRF treatment of the occipital nerve, which was used to treat occipital neuralgia.  Patients were diagnosed with occipital neuralgia according to the International Classification of Headache Disorders classification criteria.  These investigators performed PRF neuromodulation when patients presented with clinical findings suggestive occipital neuralgia with positive diagnostic block of the occipital nerves with local anesthetics.  Patients were analyzed according to age, duration of symptoms, surgical results, complications and recurrence.  Pain was measured every month after the procedure using the visual analog and total pain indexes.  From 2010, a total of 10 patients were included in the study.  The mean age was 52 years (34 to 70 years).  The mean follow-up period was 7.5 months (6 to 10 months).  Mean VAS and mean total pain index scores declined by 6.1 units and 192.1 units, respectively, during the follow-up period.  No complications were reported.  The authors concluded that PRF neuromodulation of the occipital nerve is an effective treatment for occipital neuralgia.  Moreover, they stated that further controlled prospective studies are needed to evaluate the exact effects and long-term outcomes of this treatment method.

In a randomized, double-blinded, placebo controlled trial, Taverner and colleagues (2010) examined if transcutaneous-PRF treatment (TCPRFT) was able to reduce the pain experienced by patients awaiting total knee joint replacement (TKJR).  Patients on the waiting list for assessment for TKJR were invited to participate and were examined in the clinic if they satisfied the inclusion criteria.  Patients were randomized to receive active or sham TCPRFT.  The alteration in pain and function of the treated knee after a single TCPRFT was assessed at examination at 1 and 4 weeks using VAS at rest and after 20-m and 400-m walks.  The results of 50 patients showed a statistically significant reduction in VAS at 1 and 4 weeks compared with baseline in the group who received active treatment.  These researchers also demonstrated what is considered a clinically significant improvement in this group that became more pronounced at week 4 compared with week 1 and also more after a 400-m walk compared with a 20-m walk.  Maximum improvement observed in group data was 19/100 VAS.  Patients receiving sham treatment showed no statistically significant improvement.  The authors believed this to be the first report of a controlled study of TCPRFT.  They stated that the findings of this pilot study showed a benefit of the technique that justifies future research.

Basal et al (2012) evaluated the effectiveness of PRF denervation of spermatic cord for the treatment of chronic orchialgia.  A total of 5 patients were evaluated with a thorough medical and psychiatric history, physical examination and scrotal doppler ultrasound, urinary system X-ray film and urine analysis.  One of the patients had bilateral chronic orchialgia.  All the patients had pain for at least a period more than 3 months, and multiple conservative therapies failed to alleviate the pain.  Patients, who had temporary pain relief after undergoing outpatient diagnostic cord block, were determined to be candidates for PRF denervation.  Pulsed RF denervation of spermatic cord was performed for 6 testicular units.  Visual analog scores were noted before and after the procedure.  There were no pathologic conditions that indicated chronic orchialgia in any of the patients.  No complications including testicular atrophy or hypoesthesia of the scrotal or penile skin occurred after the procedure.  Mean VAS before and after the procedure was 9 and 1, respectively.  None of the patients needed any analgesics after the procedure and during the follow-up period.  Mean follow-up period was 20 +/- 2.5 weeks.  No recurrence was noted and none of the patients needed additional therapy.  The authors concluded that this is a limited case report on the short-term use of PRF.  They stated that randomized, placebo-controlled and long follow-up period studies are needed to better assess the effectiveness of this procedure for chronic orchalgia.

In a review on "radiofrequency and pulsed radiofrequency treatment of chronic pain syndromes" van Boxem et al (2008) stated that there are currently 6 reviews on PRF for the management of spinal pain.  Two reviews on interventional pain management techniques in general also discussed RF.  The outcomes of those reviews depend on the type of studies included and the opinion of the reviewers, which may result in different evidence levels.  Radiofrequency denervation at the cervical and lumbar level has produced the most solid evidence.  The differences in treatment outcome registered in the 5 RCTs regarding lumbar facet denervation can be attributed to differences in patient selection and/or inappropriate technique.  There is insufficient evidence supporting the use of RF facet denervation for the management of cervicogenic headache.  The studies examining the management of cervical radicular pain suggested a comparable efficacy for RF and pulsed RF (PRF).  The PRF treatment is supposed to be safer and therefore should be preferred.  The superiority of RF treatment adjacent to the lumbar dorsal root ganglion for the management of lumbar radicular pain has not been demonstrated in an RCT.  Information regarding RF treatment of sacro-iliac joint pain is accumulating.  No randomized sham-controlled trials on the value of RF treatment of the Gasserian ganglion for the management of idiopathic trigeminal neuralgia have been published.  One RCT indicated superiority of RF over PRF for the management of idiopathic trigeminal neuralgia.  The authors concluded that future research to confirm or deny the efficacy of (P)RF should be conducted in carefully selected patient populations.  The tests used for patient inclusion in such a trial could potentially help the clinician in selecting patients for this type of treatment.  They also stated that the value of PRF treatment of the peripheral nerves also needs to be confirmed in well-designed trials.

Chua et al (2011) evaluated the effectiveness of PRF treatment in chronic pain management in RCTs and well-designed observational studies.  The physics, mechanisms of action, and biological effects were discussed to provide the scientific basis for this promising modality.  These investigators systematically searched for clinical studies on PRF.  They searched the MEDLINE (PubMed) and EMBASE database, using the free text terms: pulsed radiofrequency, radio frequency, radiation, isothermal radiofrequency, and combination of these.  They classified the information in 2 tables, 1 focusing only on RCTs, and another, containing prospective studies.  Date of last electronic search was May 30, 2010.  These researchers found 6 RCTs that evaluated the efficacy of PRF, 1 against corticosteroid injection, 1 against sham intervention, and the rest against conventional RF thermocoagulation.  Two trials were conducted in patients with LBP due to lumbar zygapophyseal joint pain, 1 in cervical radicular pain, 1 in lumbo-sacral radicular pain, 1 in trigeminal neuralgia, and another in chronic shoulder pain.  The authors concluded that from the available evidence, the use of PRF to the dorsal root ganglion in cervical radicular pain is compelling.  With regards to its lumbo-sacral counterpart, the use of PRF can not be similarly advocated in view of the methodological quality of the included study.  Pulsed RF application to the supracapular nerve was found to be as effective as intra-articular corticosteroid in patients with chronic shoulder pain.  The use of PRF in lumbar facet arthropathy and trigeminal neuralgia was found to be less effective than conventional RF thermocoagulation techniques.

van Boxem et al (2011) noted that lumbosacral radicular syndrome (LRS) is probably the most frequent neuropathic pain syndrome.  Three months to 1 year after onset, 30 % of the patients still experience ongoing pain.  The management of those patients is complex, and treatment success rates are rather low.  The beneficial effect of PRF therapy has been described for the treatment of LRS in case reports and in retrospective and prospective studies.  Up until now, no neurological complications have been reported after PRF treatment.  These investigators performed a clinical audit to evaluate the amount of pain relief after a single PRF treatment.  A total of 60 consecutive patients who received a PRF treatment adjacent to the lumbar-dorsal root ganglion for the management of LRS in the period 2007 to 2009 were included.  The main study objective was to measure the reduction of pain after the PRF treatment by using the global perceived effect.  The primary end point was defined as at least 50 % pain relief for a period of 2 months or longer.  The primary end point was achieved in 29.5 % of all the PRF interventions.  After 6 months, 50 % pain relief was still present in 22.9 % of the cases and after 12 months in 13.1 % of the cases.  The need for pain medication was significantly lower after PRF treatment in the success group compared with the non-success group.  The authors concluded that PRF treatment can be considered for the management of LRS patients.  Moreover, they statedthat these results need to be confirmed in a RCT.

In a systematic review, Hansen and colleagues (2012) evaluate the effectiveness of therapeutic sacro-iliac joint (SIJ) interventions.  The available literature on therapeutic SIJ interventions in managing chronic LBP and lower extremity pain was reviewed.  The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria for randomized trials of interventional techniques and the criteria developed by the Newcastle-Ottawa Scale for observational studies.  The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF).  Data sources included relevant literature published from 1966 through December 2011 that was identified through searches of PubMed and EMBASE, and manual searches of the bibliographies of known primary and review articles.  The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term relief = greater than 6 months).  Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake.  For this systematic review, a total of 56 studies were considered for inclusion.  Of these, 45 studies were excluded and a total of 11 studies met inclusion criteria for methodological quality assessment with 6 randomized trials and 5 non-randomized studies.  The evidence for cooled radiofrequency neurotomy in managing SIJ pain is fair.  The evidence for effectiveness of intra-articular steroid injections is poor.  The evidence for peri-articular injections of local anesthetic and steroid or botulinum toxin is poor.  The evidence for effectiveness of conventional RF neurotomy is poor.  The evidence for PRF is poor.  The authors concluded that the evidence was fair in favor of cooled RF neurotomy and poor for short-term and long-term relief from intra-articular steroid injections, peri-articular injections with steroids or botulin toxin, PRF, and conventional RF neurotomy.

Werner et al (2012) stated that in the United States, it is estimated that between 6,000 and 18,000 individuals each year present with disabling pain after inguinal hernia repair.  Although surgical treatment with mesh removal is one of few options available, effective alternatives to non-surgical management are needed.  The use of PFR, leading to non-destructive lesions of nerve structures, has been proposed as a treatment option.  To examine the evidence of treatment efficacy, a systematic literature search was made.  From the databases PubMed, Embase, and CINAHL, 4 case reports were retrieved and 8 patients were included for analysis.  The PFR treatment was peripheral (n = 4) and central (n = 4).  Pain relief varied between 63 % and 100 %, the follow-up period was 3 to 9 months, and no adverse effects or complications were reported.  The authors concluded that the evidence base of PRF in persistent pain following inguinal herniotomy is fairly limited.  They also presented suggestions for improved research strategies in this field. 

Taverner et al (2013) reported a retrospective audit of transcutaneous PRF treatment therapy (TCPRFT) for shoulder pain over a 4-year period.  Electronic and manual case review revealed that TCPRFT had been performed on 13 patients, with 15 painful shoulders, using a single treatment session between 2006 and 2010 in an out-patient setting.  Of the 15 shoulders treated, 10 had pain relief for over 3 months with an average pain score reduction of 6.1 of 10 and an average duration of pain relief of 395 days.  Two experienced pain relief of less than 3 months with an average reduction in pain score of 4.3 of 10 and an average duration of effect of 11 days.  Three cases experienced no pain relief from the treatment.  These results suggested TCPRFT may provide clinically useful pain relief and be another treatment modality for shoulder pain.  The authors concluded that these findings justifies further research, and they are proceeding with a double-blind placebo RCT to determine the effectiveness of TCPRFT in chronic shoulder pain.

Fang et al (2014) examined the effectiveness and clinical utility of CT-guided PRF for treatment of trigeminal neuralgia (TN).  Patients who were diagnosed with severe TN between September 2010 and October 2010 were included.  Pulsed radiofrequency treatment was employed to treat TN.  To verify the accurate needle position, a thin-section cranial CT scan was performed by using a multi-detector CT scanner.  Three-dimensional reconstruction was performed to visualize the location of the needle and the foramen ovale.  A total of 20 patients were included in the study.  Seven patients (35 %) had favorable outcome 1 year after the PRFT.  The numeric rating scale in the 7 patients with good outcome was significantly lower than the 13 patients with bad outcome at 1 day, 1 week, and 2 weeks after the treatment.  The remaining 13 patients had residual pain 2 weeks after the PRFT and had to receive RF thermo-coagulation (RFTC).  The authors concluded that these findings demonstrated that CT-guided PRFT is not an effective method of pain treatment for idiopathic TN as compared with conventional RFTC.  However, CT-guided PRFT is associated with less complication than RFTC.

Rana and Matchett (2013) stated that pain associated with cancer is often difficult to treat, even more so when tumors involve peripheral nerves.  Therapy is complex and often requires a multi-modal approach that can include medications, radiation, and interventional techniques.  These components are utilized with variable success, but are also limited by known complications or adverse effects.  These investigators presented the case of a 53-year old woman with a metastatic axillary tumor that involved her brachial plexus.  Attempts to control her pain with medication were unsuccessful despite escalation and use of adjunct agents.  She was not deemed to be a surgical candidate due to the size and location of the tumor.  Radiation was discussed but, obviously, would not work immediately.  These investigators decided to employ a brachial plexus catheter for continuous nerve block, which provided almost complete relief of pain.  Since her pain was deemed to be of peripheral etiology, PRF ablation of her brachial plexus was used for more long-term pain relief.  The patient responded very well with minimal pain issues and no apparent complications.  On follow-up, the patient had good relief for almost 2 months.  Pulsed radiofrequency is a poorly understood technology that has increasing evidence for certain pain conditions; however, for cancer and peripheral nerves the evidence is slim to none.  The authors noted that this case presented a successful use for pain management of a brachial plexopathy due to a tumor.  They proposed that PRF may present a non-neurodestructive pain management technique for tumors involving peripheral nerves, although more data are definitely needed.

Bui et al (2013) reported on the utility of a pudendal nerve block by PRF ablation for the treatment of male pelvic pain and urinary urgency and hesitancy.  The patient was an 86-year old man with a 30-year history of urinary hesitancy and urgency.  The patient also had pain in the area of the perineum but considered it a secondary issue.  The patient was seen by a number of specialists, tried various medications, and underwent a variety of procedures to no avail.  Therefore, the patient underwent a PRF ablation of the pudendal nerve.  The patient reported marked improvement in his pelvic pain as well as a drastic reduction in his urinary urgency and hesitancy.  The authors concluded that urinary urgency and hesitancy and male pelvic pain are some of the most common symptoms affecting men.  Pudendal nerve block by PRF ablation is an effective treatment of pelvic pain.  It may also hold some therapeutic value in the treatment of urinary urgency and hesitancy as this case demonstrated.  Moreover, they stated that further studies are needed to help clarify both the anatomy of the pelvis as well as if pudendal blocks are effective in treating more than pelvic pain.

Kestranek et al (2013) described a new treatment of refractory severe vulvodynia.  These researchers reported on the successful use of the PRF treatment in a patient with intractable chronic vulvodynia.  To the authors’ knowledge, this is the first report of a successful use of PRF in the treatment of chronic vulvodynia.  They concluded that if the effectiveness of PRF is confirmed by more studies, it would be a welcome addition to the treatment modalities used to treat this sometimes truly intractable condition.

The American Society of Interventional Pain Physicians’ updated guidelines on “Interventional techniques in chronic spinal pain” (Manchikanti et al, 2013) noted that the evidence is limited for pulsed radiofrequency neurotomy as a therapeutic lumbar facet joint interventions; and the evidence is limited for both pulsed radiofrequency and conventional radiofrequency neurotomy as a therapeutic sacroiliac joint interventions.

Schianchi et al (2013) evaluated the effectiveness of intra-articular (IA) PRF in a group of 57 consecutive patients with chronic joint pain.  Patients with intractable joint pain for more than 6 months were treated with IA PRF 40 to 45 V for 10 to 15 mins in small joints and 60 V for 15 mins in large joints using fluoroscopic confirmation of correct needle position.  A total of 28 shoulders, 40 knees, 10 trapezio-metacarpal, and 11 first metatarso-phalangeal joints were treated.  Results were evaluated at 1, 2, and 5 months.  The procedure was repeated after 1 month in 10 patients with initial suboptimal results.  Success was defined as a reduction of pain score by at least 50 %.  All groups showed significant reductions in pain scores at all 3 follow-up visits.  Success rates were higher in small joints (90 % and 82 %, respectively) than large ones (64 % and 60 %, respectively).  Interestingly, IA PRF was successful in 6 out of 10 patients who had undergone previous surgery, including 3 with prosthetic joint replacement and in 6 of the 10 repeated procedures.  There were no significant adverse effects or complications.  The authors concluded that IA PRF induced significant pain relief of long duration in a majority of the patients with joint pain.  The exact mechanism is unclear, but may be related to the exposure of immune cells to low-strength RF fields, inducing an anti-inflammatory effect.  The success rate appears to be highest in small joints.  The authors recommended additional research including control groups to further investigate and clarify this method; these data suggested that PRF may represent a useful modality in the treatment of arthrogenic pain.

Kim and colleagues (2014) noted that amputation neuroma can cause very serious, intractable pain.  Many treatment modalities are suggested for painful neuroma.  Pharmacologic treatment shows a limited effect on eliminating the pain, and surgical treatment has a high recurrence rate.  These investigators applied PRF treatment at the neuroma stalk under ultrasonography guidance.  The long-term outcome was very successful, prompting these researchers to report this case.  These preliminary findings from a single-case study need to be validated by well-designed studies.

Terkawi and Romdhane (2014) stated that chronic orchalgia is a frustrating clinical problem for both the patient and the physician.  These researchers presented a 17-year old boy with a bilateral idiopathic chronic intractable orchalgia with failed conservative treatment.  For 2 years, he suffered from severe attacks of scrotal pain that affected his daily activities and caused frequent absence from school.  These investigators performed ultrasound-guided PRF ablation of the genital branches of the genito-femoral nerve after local anesthetic nerve block confirmed the diagnosis and yielded 6 weeks of symptom relief.  The authors noted that 7-month follow-up revealed complete satisfactory analgesia.  The clinical value of this non-invasive approach to treat intractable chronic orchalgia needs to be further researched.

Park et al (2014) noted that post-herpetic neuralgia (PHN) is one of the most difficult pain syndromes to treat.  Invasive treatments may be considered when patients fail to obtain adequate pain relief from noninvasive treatment approaches.  These researchers presented 3 cases of PHN in the mandibular branch treated with ultrasound-assisted mental nerve block and PRF treatment.  None of the patients had adequate pain relief from the medical therapy, so these investigators performed the mental nerve block on the affected side under ultrasound assistance.  Two patients showed satisfactory pain relief continuously over 12 months without any further interventions, whereas 1 patient only had short-term pain relief.  For the patient who had short-term pain relief, these researchers performed PRF treatment on the left mental nerve under ultrasound assistance.  After PRF treatment, the patient had adequate pain relief for 6 months and there was no need for further management.  These preliminary findings from a single patient need to be validated by well-designed studies.

Chon and colleagues (2014) stated that tarsal tunnel syndrome (TTS) is a compression neuropathy that results from entrapment of the posterior tibial nerve or its branches.  Tarsal tunnel syndrome may be treated either by conservative measures, including physical therapy, medications, and steroid injections, or by surgical decompression.  Despite a variety of treatments, a few cases of TTS will relapse, and many cases of recurrent TTS will require re-operation.  These researchers reported a new application of ultrasound-guided PRF in 2 cases of intractable TTS.  Both patients had a long duration of severe foot pain and had been treated with various therapeutic modalities without lasting relief.  These investigators applied ultrasound-guided PRF to the affected posterior tibial nerve in each patient, and both had significantly reduced pain intensity scores and analgesic requirements without any complications.  The authors concluded that ultrasound-guided PRF for intractable TTS relieved severe foot pain; it may supersede surgery as a reliable treatment for intractable TTS.  These preliminary findings need to be validated by well-designed studies.

Nagar and colleagues (2015) investigate the clinical utility of RF neurotomy, and PRF ablation for the management of cervicogenic headache (CHA).  The review included relevant literature identified through searches of PubMed, Cochrane, Clinical trials, U.S. National Guideline Clearinghouse and EMBASE from 1960 to January 2014.  The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria for RCTs and the Newcastle-Ottawa Scale criteria for observational studies.  The level of evidence was classified as good, fair, and poor based on the quality of evidence.  The primary outcome measures were reduction in pain scores and improvement in quality of life.  The primary outcome measures were headache relief and improved quality of life.  A total of 25 studies were identified for full text review; of these, 9 studies met inclusion criteria.  There were 5 non-randomized, among them 4/5 were of moderate quality, 3/5 showed RF ablation and 1/5 showed PRF as an effective intervention for CHA.  There were 4 randomized trials among them 2/4 were of high quality, 3/4 investigated RF ablation as an intervention for CHA, 1/4 investigated PRF ablation as an intervention for CHA and none of the randomized studies showed strong evidence for RF and PRF ablation as an effective intervention for CHA.  The authors concluded that there is limited evidence to support RF ablation for management of CHA as there are no high quality RCTs and/ or multiple consistent non-RCTs without methodological flaws.  They also noted that there is poor evidence to support the use of PRF for the treatment of CHA as there are no high quality RCTs or non-RCTs.

Face and Head Pain

Akbas et al (2016) retrospectively evaluated the satisfaction of PRF treatment in patients suffering from chronic face and head pain.  Infra-zygomatic approach was used for the PRF of the spheno-palatine ganglion under fluoroscopic guidance.  After the tip of the needle reached the target point, 0.25 to 0.5 ms pulse width was applied for sensory stimulation at frequencies from 50 Hz to 1 V.  Paraesthesias were exposed at the roof of the nose at 0.5 to 0.7V.  To rule out trigeminal contact that led to rhythmic mandibular contraction, motor stimulation at a frequency of 2 Hz was applied.  Then, 4 cycles of PRF lesioning were performed for 120s at a temperature of 42° C.  Pain relief could not be achieved in 23 % of the patients (unacceptable), whereas pain was completely relieved in 35 % of the patients (excellent) and mild-to-moderate pain relief could be achieved in 42 % of the patients (good) through spheno-palatine ganglion-PRF treatment.  The authors concluded that PRF of the spheno-palatine ganglion is effective in treating the patients suffering from intractable chronic facial and head pain.  Moreover, they stated that there is a need for prospective RCTs in order to confirm the safety and effectiveness of this new treatment modality in chronic face and head and pain.

Inguinal Neuralgia

In a randomized, double-blind controlled trial, Makharita and Amr (2015) evaluated the effectiveness of PRF in management of chronic inguinal neuralgia.  A total of 21 patients were allocated into 2 groups.  Group 1 received 2 cycles of PRF for each nerve root.  In Group 2, after stimulation, these researchers spent the same time to mimic PRF.  Both groups received bupivacaine 0.25 % +' 4 mg dexamethasone in 2 ml for each nerve root; VAS was assessed.  Duration of the first block effective pain relief was reported.  Repeated PRF blockade was allowed for any patient who reported a VAS greater than 30 mm in both groups during the 1 year follow-up period.  The number and duration of blocks were reported and adverse effects were also reported.  Significantly longer duration of pain relief was noticed in Group 1 (p = 0.005) after the first block, while the durations of pain relief of the second block were comparable (p = 0.59).  In Group 1 the second PRF produced pain relief from the 24th week until the 10th month while in Group 2, pain relief was reported from the 16th week until the 8th month after the use of PRF.  All patients in Group 2 received 3 blocks (the first was a sham PRF) during the 1 year follow-up period.  Meanwhile, 2 PRF blocks were sufficient to achieve pain relief for patients in Group 1 except 4 patients who needed a third PRF block.  No adverse events were reported.  The authors concluded that for intractable chronic inguinal pain, PRF for the dorsal root ganglion represents a promising treatment modality.  The main drawback of this study was its small sample size (n = 20)

Morton’s Neuroma

Deniz and associates (2015) stated that Morton's neuroma is a perineural fibrosis of an inter-metatarsal plantar nerve.  Burning, numbness, paresthesia, and tingling down the interspaces of involved toes may also be experienced.  Taking into account all of this information, these researchers designed a prospective open-label study to evaluate the effectiveness of PRF on Morton's neuroma.  A total of 20 patients with Morton's neuroma were experiencing symptomatic neuroma pain in the foot not relieved by routine conservative treatment.  All of the patients had been evaluated by a specialized orthopedist and were offered PRF as a last option before having surgery.  Initially, pain level (numerical rating scale), successful pain control (a greater than or equal to 50 % pain decrease was accepted as successful pain control), comfort when walking (yes or no), and satisfaction level (satisfied or not satisfied) were evaluated.  These investigators reported a decrease in the pain level in 18 of 20 patients, successful pain control in 12, and wearing shoes and walking without pain in 16.  Overall, satisfaction was rated as excellent or good by 12 patients with Morton's neuroma in this series.  The authors concluded that these findings indicated that ultrasound-guided PRF is a promising treatment modality in the management of Morton's neuroma pain.

Post-Herpetic Itch

Ding and colleagues (2014) reported the findings of a patient with intractable post-herpetic itch lasting for 1 year.  The itch was mainly from the left vertex, frontal and ophthalmic regions and extended to the left neck area.  The patient had negative response to the ophthalmic nerve block.  Under the initial positive response to the great occipital nerve block, PRF was performed on the position of the great occipital nerve.  After 4 months treatment, the itch was completely vanished.  The authors concluded that this case study demonstrated the effectiveness of PRF for intractable post-herpetic itch originating in the head and neck.  However, they stated that more patients are needed to verify this management.

Thoracic Pain

In a retrospective data analysis involving 49 patients, Cohen et al (2006) compared treatment outcomes between pharmacotherapy, PRF of the intercostal nerves (ICN) and PRF of the dorsal root ganglia (DRG) in chronic postsurgical thoracic pain (CPTP).  At 6-week follow-up, 61.5 % of the PRF DRG group reported greater than or equal to 50 % pain relief versus 27.3 % in the medical management (MM) group and 21.4 % in the IC group (p = 0.12).  At 3-month follow-up, 53.8 % in the DRG group continued to report greater than or equal to 50 % pain relief versus 19.9 % in the MM and 6.7 % in the ICN groups, respectively (p = 0.02).  Among the PRF patients who did report a successful outcome, the mean duration of pain relief was 2.87 months in the ICN group and 4.74 months in the DRG group (p = 0.01).  The authors concluded that PRF of the DRG was a superior treatment to pharmacotherapy and PRF of the ICN in patients with CPTP.  Moreover, they stated that prospective studies are needed to confirm these results and identify the best candidates for this treatment.

In a prospective, randomized, double-blinded study, Ke and colleagues (2013) examined the safety and effectiveness of PRF for treating thoracic PHN through the puncture of the angulus costae.  A total of 96 patients with thoracic (T2-L1) PHN were equally randomized assigned into 2 groups.  The electrode needle punctured through the angulus costae of each patient guided by x-ray; PRF at 42° C for 120 seconds was applied after inducing paresthesia involving the affected dermatome area.  Pulsed RF was applied in the PRF group (n = 48) twice.  It was also applied in the sham group (n = 48) twice without RF energy output.  The treatment was done once-weekly for 3 weeks.  Tramadol was used for flare pain when the VAS was greater than or equal to 3.  The therapeutic effect was evaluated by VAS, SF-36 health survey questionnaire, side effects (type, frequency, and onset time) before treatment, at days 3, 7, and 14, and at months 1, 2, 3 and 6 after PRF.  The average of tramadol (mg/day) administered within the 1st month after treatment was also recorded.  The post-procedure VAS scores in the PRF group were significantly lower than those in the sham group and lasted for 6 months after treatment (p < 0.05).  The SF-36 score, such as physical functioning, physical role, pain, general perceptions of health, social function, emotional role, and mental health index were significantly improved until 6 months after treatment in the PRF group compared to the sham group (p < 0.01 to 0.05).  The average dosage of tramadol administrated (mg/day) within the 1st month after treatment was also significantly reduced in the PRF group compared to the sham group (p < 0.05).  There were no obvious signs of pneumothorax, bleeding, infection, or other severe side effects in either group (p > 0.05).  The authors concluded that the strategy that the angulus costae be used as the PRF puncture point of an electrode needle and the final localization of the needle tip as determined by sensory testing was an effective and safe therapeutic alternative for thoracic PHN treatment.  They stated that the benefits included that the procedure was minimally invasive, provided short-term pain relief, and improved quality of life.  The main drawbacks of this study were its single-center study, relatively small number of patients, and mid-term follow-up duration (6 months).

The Work Loss Data Institute’s guideline on “Low back -- lumbar & thoracic (acute & chronic)” (2013) listed PRF treatment as one of the interventions/procedures were considered, but are not recommended.

Gulati et al (2015) noted that tumors invading the chest wall and pleura are often incurable, and treatment is targeted toward palliation of symptoms and control of pain.  When patients develop tolerance or side effects to systemic opioid therapy, interventional techniques can better optimize a patient's pain.  These investigators performed a retrospective review of 146 patients from April 2004 to January 2014 who underwent diagnostic and therapeutic procedures for pain relief.  Using 4 patients as a paradigm for neurolytic approaches to pain relief, these researchers presented a therapeutic algorithm for treating patients with intractable thoracic chest wall pain in the oncologic population.  For each patient, these researchers described the use of intercostal/paravertebral nerve blocks and neurolysis, pulsed radio-frequency ablation (PRFA) of the thoracic nerve roots, or intrathecal pump placement to successfully treat the patient's chest wall pain.  Analysis of 146 patient charts was also performed to assess effectiveness of therapy.  A total of 79 % of patients undergoing an intercostal nerve diagnostic blockade (with local anesthetic and steroid) stated that they had improved pain relief with 22 % having prolonged pain relief (average of 21.5 days).  Only 32 % of successful diagnostic blockade patients elected to proceed to neurolysis, with a 62 % success rate; 7 patients elected to proceed to intrathecal drug delivery.  The authors concluded that intercostal nerve diagnostic blockade with local anesthetic and steroid may lead to prolonged pain relief in this population.  Furthermore, depending on tumor location, the authors have developed a paradigm for the treatment of thoracic chest wall pain in the oncologic population.  Puled RF ablation was not discussed as a successful means of treating thoracic chest wall pain associated with tumors.

In summary, there is currently insufficient evidence to support the use of PRF in the treatment of various chronic pain syndromes.  Well-designed studies (prospective, randomized, placebo-controlled trials with large sample size and long-term follow-up) are needed to ascertain the clinical value of this approach.

Diabetic Peripheral Neuropathy

Naderi and associates (2015) compared the effectiveness of transcutaneous electrical nerve stimulation (TENS) and PRF lumbar sympathectomy in treating painful diabetic peripheral neuropathy (DPN). A total of 65 patients with painful DPN refractory to conventional treatment were randomly and evenly assigned to either the TENS or PRF lumbar sympathectomy groups.  Pain evaluations were based on the 10-point NRS.  Subjects were followed for 3 months and had a total of 4 study visits (baseline and 1 week, 1 month, and 3 months after treatment); 60 patients completed all study visits.  In both groups, the NRS rating significantly decreased after treatment, with a marked pain reduction observed at the first follow-up evaluation.  In the PRF group, the NRS decreased from 6.46 at baseline to 2.76 at the 1 week visit.  One and 3 months after treatment, the NRS was 4.30 and 5.13, respectively (p < 0.0001).  In the TENS group, the NRS decreased from 6.10 at baseline to 3.96 at the 1 week visit.  One and 3 months after treatment, the NRS was 5.23 and 5.90, respectively (p < 0.0001).  Unfortunately, the NRS steady increased almost back to baseline levels in the TENS group.  The NRS only slightly increased during the follow-up period in the PRF group, but did not reach baseline levels.  The authors concluded that both TENS and PRF lumbar sympathectomy are promising pain relief treatments for painful DNP.  However, PRF lumbar sympathectomy appeared to have a superior efficacy.  They stated that further studies with a larger sample size and a longer follow-up period are needed.

Striae Rubra

Karia and colleagues (2016) noted that striae are linear atrophic depressions that form in areas of dermal damage in the skin. Currently, no consensus or protocol exists for the treatment of stria rubra.  Topical retinoids, chemical peels, microdermabrasion, radiofrequency, photothermolysis, intense pulsed light and lasers are some of the modalities used.  These researchers compared the effectiveness of various therapeutic modalities in striae rubra.  This prospective cohort study comprised of a total of 50 patients from August 2012 to October 2013 in a tertiary care center in Western India, Gujarat having striae rubra.  They were randomly divided into 5 groups of 10 patients each.  Patients were evaluated on the basis of visual assessment, both by doctor as well as the patient.  Group I was given topical tretinoin (0.1 % w/w) gel applied once at night, Group II: microdermabrasion (MDA) combined with trichloroacetic acid (TCA) (30 %) peel, Group III: mesotherapy, Group IV: Q-switched Nd: YAG laser, and Group V-combination treatment of microdermabrasion, salicylic acid peel and retinol (yellow) peel.  Patients were treated at an interval of 15 days for 2 months and then at monthly intervals.  Objective assessment was done at 2nd month, 6th month, and at the end of 1st year.  Patients in Group I treated with topical tretinoin showed the least response with 80 % (n = 8) of them showing minimal clinical improvement (0 to 25 %) as compared to patients in Group V in which 60 % (n = 6) patients showed moderate clinical improvement (50 to 75 %).  While the majority of the patients in Group II, III, and IV showed mild clinical improvement (25 to 50 %).  The authors concluded that striae rubra is a common cause of concern for adolescent population.  Combination treatment with microdermabrasion, salicylic acid and retinol yellow peel gave superior results as compared to other therapeutic options.  Mild-to-moderate improvement was seen with Nd: YAG laser, mesotherapy and MDA + TCA whereas minimal improvement were seen with topical tretinoin.

Vaginismus

Carvalho and co-workers (2017) stated that vaginismus is a poorly understood disorder, characterized by an involuntary muscular spasm of the pelvic floor muscles and outer third of the vagina during intercourse attempt, which results in aversion to penetration. It is reported to affect 1 % to 7 % of women worldwide.  The authors described the case of a young patient with vaginismus in whom techniques usually from the chronic pain domain (e.g., PRF and trigger point infiltration) were used as part of her multi-modal therapeutic regimen.  The clinical benefit of PRF for the treatment of vaginismus needs to be further investigated.

Ventricular Arrhythmias (Fibrillation or Tachycardia)

Hayase and associates (2016) stated that there is increasing interest in interventional therapies targeting the cardiac sympathetic nervous system to suppress ventricular arrhythmias. In this case report, these researchers described an 80-year old patient with ischemic cardiomyopathy and multiple implantable cardioverter-defibrillator shocks due to refractory ventricular tachycardia and ventricular fibrillation who was unable to continue bi-weekly stellate ganglion block procedures using bupivacaine 0.25 % for suppression of his arrhythmias.  He had previously failed anti-arrhythmic drug therapy with amiodarone, catheter ablation, and attempted surgical autonomic denervation.  He underwent PR  treatment (3 lesions, 2 minutes each, temperature 42°C, 2-Hz frequency, 20-millisecond pulse width) of the left stellate ganglion resulting in persistent arrhythmia suppression for more than 12 months duration.  This represented the first report of a PR stellate ganglion lesion providing long-term suppression of ventricular arrhythmias.  The authors concluded that further study of this technique in patients with refractory ventricular tachycardia or ventricular fibrillation is needed.

Coccydynia

Chen and colleagues (2017) stated that coccydynia is a condition with a multitude of different causes, characterized by ill-defined management. There are multiple prospective studies, including several controlled trials, that have evaluated conservative therapies.  Additionally, a plethora of observational studies have assessed coccygectomy, but few studies have reported results for non-surgical interventional procedures.  In this report, these investigators described the results of 12 patients who received conventional or PRF for coccydynia and systematically reviewed the literature on management.  They performed a retrospective data analysis evaluating patients who underwent PRF or conventional RF at Johns Hopkins Hospital and Walter Reed National Military Medical Center.  These researchers also performed a comprehensive literature review to contextualize these results.  The mean age of patients treated was 50.25 years (SD = 11.20 years, range of 32 to 72 years), with the mean duration of symptoms being 3.6 years (SD = 3.36 years, range of 1 to 10 years).  There were 10 men and 2 women in this cohort.  Among patients who received RF treatment, the average benefit was 55.5 % pain relief (SD = 30.33 %, range of 0 to 100 %).  Those who underwent conventional RF(versus PRF) and who received prognostic blocks were more likely to experience a positive outcome.  There were 2 cases of neuritis, which resolved spontaneously after several weeks.  The authors concluded that RF ablation of the sacrococcygeal nerves may serve as a useful therapeutic option for patients with coccydynia who have failed more conservative measures.  Moreover, they stated that further research into this therapeutic approach and its benefit for coccydynia should incorporate a control group for comparison.

Interstitial Cystitis

Kim and associates (2016) stated that a variety of therapeutic modalities are available for the treatment of interstitial cystitis.  However, among them, the less invasive therapies are usually ineffective, whereas the invasive ones carry potential risks of serious side effects and complications.  They noted that PRF treatment of the superior hypogastric plexus may be an alternative to conventional treatments, as it provides non-destructive neuromodulation to the superior hypogastric plexus, which transmits the majority of pain signals from the pelvic viscera.  For 7 years, a 35-year old female patient had been experiencing lower abdominal pain provoked by urinary bladder filling, peri-vulvar pain developing spontaneously during sleep or upon postural change, urinary urgency and frequency with 15- to 60-min intervals between urinations, and nocturia with 10 voids per night.  Hydro-distension of the bladder, monthly intra-vesical administration of sterile sodium chondroitin sulfate, and oral medications including gabapentin and pentosan polysulfate had not been effective in managing the pain and symptoms.  Given the satisfactory result of a diagnostic block of the superior hypogastric plexus, 2 sessions of PRF treatment of the superior hypogastric plexus, which applied RF pulses with a pulse frequency of 2 Hz and a pulse width of 20 ms for 120 seconds twice per session to maintain the tissue temperature near the electrode at 42° C, were performed at a 6-month interval.  This treatment relieved the pain and symptoms for 2 years and 6 months.  The authors stated that a prospective RCT is needed to confirm the safety and effectiveness of this procedure for the treatment of interstitial cystitis.

Meralgia Paresthetica

In a retrospective study, Lee and colleagues (2016) evaluated clinical outcomes of PRF neuromodulation of the lateral femoral cutaneous nerve (LFCN) in meralgia paresthetica (MP) patients refractory to conservative treatment.  These investigators reviewed the clinical data of 11 patients with medically intractable MP who underwent PRF neuromodulation of the LFCN.  These patients with MP underwent a diagnostic LFCN block using 2.0 % lidocaine.  Temporary pain relief greater than 50 % was considered to be a positive response to the diagnostic nerve block.  Following a positive response to the diagnostic nerve block, patients underwent PRF neuromodulation at 42 degrees for 2 minutes.  Patient pain was evaluated using a 10-cm VAS.  In MP patients who received PRF, these researchers statistically evaluated VAS scores and the presence of any complications for 6 or more months after the procedure.  The mean initial patient VAS score was 6.4 ± 0.97 cm.  This score was decreased to 0.91 ± 0.70 cm, 0.82 ± 0.75 cm, and 0.63 ± 0.90 cm at the 1-, 3-, and 6-month follow-ups, respectively (p < 0.001); 63.6 % of patients achieved complete pain relief (pain-free) in the last follow-up, whereas 27.3 % of patients achieved successful pain relief (= 50 % reduction in pain as determined by the VAS score).  Furthermore, these researchers did not observe any complications after the procedure.  The authors concluded that PRF neuromodulation of the LFCN provided immediate and long-lasting pain relief without complications.  They stated that PRF of the LCFN can be used as an alternative treatment in patients with MP who are refractory to conservative medical treatment.

The authors noted that this study had several drawbacks. It was not a randomized, controlled study, but a retrospective case series involving a small sample (n = 11).  Thus, the outcomes of this study may not be generalizable.  Additionally, the only outcome measure was determined using a pain assessment scale; however, LFCN neuropathy can influence the patient’s functional status, including mobility.  Future studies should also evaluate patients’ global QOL during the follow-up period.  However, although this study was retrospective, it provided a promising view of the effectiveness and safety of PRF in patients with refractory MP.  They stated that future placebo-controlled, randomized, and double-blind studies may provide more objective information on the effectiveness of PRF in patients with MP.

Myofascial Pain Syndrome of the Gastrocnemius / Trapezius Muscle

Park and co-workers (2016) compared the effects of ultrasound-guided PRF treatment (UG-PRF) in the gastrocnemius inter-fascial space and ultrasound-guided inter-fascial injection (UG-INJ) on myofascial pain syndrome (MPS).  A total of 40 consecutive patients with MPS of the gastrocnemius were enrolled and were allocated to either of the 2 groups
  1. 20 patients were treated by UG-PRF delivered to the gastrocnemius inter-fascial space (UG-PRF group) and
  2. the other 20 patients were treated by inter-fascial injection (UG-INJ group).  
The primary outcome measure was the NRS for pain on pressing the tender point in the gastrocnemius, and the secondary outcome measure was health-related QOL as determined by SF-36; NRSs were obtained at the 1st visit, immediately after treatment, and at 2 and 4 weeks post-treatment, and physical component summary scores (PCS) and mental component summary scores (MCS) of the SF-36 questionnaire were measured at the 1st visit and at 4 weeks post-treatment.  Immediately after treatments, mean NRS in the UG-PRF group was significantly higher than that in the UG-INJ group (p < 0.0001).  However, at 2 and 4 weeks post-treatment, the mean NRS was significantly lower in the UG-PRF group (both p < 0.0001).  Similarly, at 4 weeks post-treatment, mean PCS and MCS were significantly higher in the UG-PRF group (p < 0.0001 and p = 0.002, respectively).  The authors concluded that ultrasound-guided gastrocnemius inter-fascial PRF provided an attractive treatment for MPS of the gastrocnemius.
This study had several drawbacks
  1. it was a single-center study with a small sample size (n = 20 for ultrasound-guided PRF treatment),
  2. the follow-up period was short ( 4 weeks), thus, the long-term effect of PRF could not be determined,
  3. the study lacked a control group to circumvent questions regarding therapeutic effects versus spontaneous symptom resolution and it was not a double-blind study due to the difference between 2 treatments.  In future studies, it is necessary to compare the PRF treatment group with a sham treatment group,
  4. the study subjects were enrolled at a university hospital and were more likely to have severe symptoms, and
  5. in this study, the explanation for the therapeutic effect and impact range of inter-fascial PRF was insufficient.  
These investigators stated that in order to achieve a greater persuasive power regarding this conclusion, further research on the nerve in the inter-fascial space and PRF effects is needed.

Cho and associates (2017) examined the effects of ultrasound (US)-guided PRF stimulation on the inter-fascial area of the trapezius muscle (TM).  These investigators also compared the effect of US-guided PRF stimulation with that of inter-fascial block (IFB) with 10 ml of 0.6 % lidocaine on the inter-fascial area of the TM.  A total of 36 patients with MPS of the TM were included and randomly assigned into 2 groups: 18 patients underwent PRF stimulation on the inter-fascial area of the TM (PRF group) and 18 patients underwent IFB with lidocaine on the same area (IFB group).  Pain intensity was evaluated using a NRS at pre-treatment, 2, 4, and 8 weeks after treatment.  At pre-treatment and 8 weeks after treatment, QOL was assessed using the SF-36, which includes the PCS and the MCS; 1 patient in the PRF group was lost to follow-up.  Patients in both groups showed a significant decrease in NRS scores at 2, 4, and 8 weeks after treatments and a significant increase in PCS and MCS of the SF-36 at 8 weeks after treatments.  Two weeks after each treatment, the decrements of NRS scores were not significantly different between the 2 groups.  However, 4 and 8 weeks after the procedures, these researchers found that the NRS score was significantly lower in the PRF group than in the IFB group.  At 8 weeks after the treatments, PCS and MCS of the SF-36 in the PRF group were significantly higher than those in the IFB group.  For the management of MPS of the TM, US-guided inter-fascial PRF had a better long-term effect on reducing the pain and the QOL compared to US-guided IFB.  The authors concluded that US-guided PRF stimulation on the inter-fascial area of the TM could be a beneficial alternative to manage the pain following MPS of the TM.

This study had several drawbacks
  1. small sample size (n = 36),
  2. short-term follow-up -- these researchers evaluated the effects of PRF and IFB in only 8 weeks.
  3. they could not clearly explain the mechanism of action of PRF in reducing pain induced by MPS, and
  4. the lack of a placebo group.  
These investigators stated that further studies are needed to address these drawbacks.

Ophthalmic Neuralgia

Bhatjiwale and colleagues (2016) examined the potential of PRF for a prolonged duration in a highly sensitive anatomic neural location, however, in a very secure, structured, and staged manner.  A patient suffering from ophthalmic division (V1) medically uncontrolled neuralgia with a pre-operative VAS score of 9/10 was subjected to a percutaneous pain relief procedure.  The patient was treated with prolonged duration PRF for 40 minutes, with corneal sensation monitoring under conscious sedation keeping a low voltage (7 V) and tip temperature at 37° C.  The patient obtained immediate relief, which was verified on the operation table itself.  Post-operative VAS score of 0/10 was recorded.  More than 6 months after the procedure, the patient was completely free from neuralgic pain and continued to have a VAS score of 0/10.  The authors concluded that as opposed to conventional PRF where mostly a tip temperature of 42° C and high voltage have been used for 2 to a maximum of 8 minutes, PRF with a tip temperature of 37° C and a safe voltage of 7 V over an ultra-extended duration of 40 minutes could give a more distinct and effective but equally safe result.  They stated that although this case verified the safety and effectiveness of prolonged duration PRF in sensitive anatomic locations, well-designed studies are needed to establish this approach as a standard treatment.

Sensory Deficits Following Stroke

Apiliogullari and colleagues (2017) noted that the integrity of the somatosensory system is important for motor recovery and neuroplasticity after strokes.  Peripheral stimulation or central stimulation in patients with central nervous system (CNS) lesions can be an effective modality in improving function and in facilitating neuroplasticity.  These researchers presented 2 hemiplegic cases with sensory motor deficit and the result of the PRF electrical stimulation to the dorsal root ganglia.  After PRF electrical stimulation, significant improvement was achieved in the patients with superficial and deep sensation.  However, during the follow-up visits the effect of PRF electrical stimulation disappeared.  The authors concluded that these preliminary results could be used in the development of future prospective cohort studies and RCTs that focus on the effect of PRF electrical stimulation on dorsal root ganglia to treat sensory deficits in post-stroke patients.

The Stimpod NMS460 Nerve Stimulator

Stimpod NMS460 (Xavant Technology) is an non-invasive neuromodulation device that applies a unique, patented PRF waveform to the affected area transcutaneously for the relief of chronic intractable pain.  This waveform creates electromagnetic effects similar to invasive PRF treatments.  The Stimpod NMS460 also incorporates nerve-locating technology.  Its "stimulation probe" is designed to direct the current to a particular nerve or region, such as a joint or muscle.  It enables practitioners to evaluate the treatment progress of damaged nerves.  The Stimpod NMS460 waveform provides all the generally accepted advantages of a normal transcutaneous electrical nerve stimulation (TENS) device, with the added advantageous of PRF. 

On January 18, 2017, the Food and Drug Administration (FDA) cleared the Stimpod NMS460 for symptomatic relief and management of chronic intractable pain and/or as an adjunctive treatment in the management of post-surgical pain, post traumatic acute pain problems, as well as an adjunct for pain control due to rehabilitation.  The Stimpod NMS460 nerve stimulator offers 2 types of waveforms for the management of pain
  1. the first is a monophasic square wave, which is typical of normal TENS machines, and
  2. the second waveform is a hybrid RF waveform that consists of a monophasic square wave with a super-imposed RF waveform. 
This waveform is proprietary and is unique to Stimpod NMS460 nerve stimulator.

However, there is insufficient evidence on the clinical value of the Stimpod NMS460.

Tsui and colleagues (2013) stated that current methods of assessing nerve blocks, such as loss of perception to cold sensation, are subjective at best.  Transcutaneous nerve stimulation is an alternative method that has previously been used to measure the current perception threshold (CPT) in individuals with neuropathic conditions, and various devices to measure CPT are commercially available.  Nevertheless, the device must provide reproducible results to be used as an objective tool for assessing nerve blocks.  In an observational study, these researchers recruited 10 healthy volunteers to examine CPT reproducibility using the Neurometer and the Stimpod NMS450 peripheral nerve stimulator.  Each subject's CPT was determined for the median (2nd digit) and ulnar (5th digit) nerve sensory distributions on both hands - with the Neurometer at 5-Hz, 250-Hz, and 2,000-Hz and with the Stimpod at pulse widths of 0.1 msec, 0.3 msec, 0.5 msec, and 1.0 msec, both at 5-Hz and 2-Hz.  Intra-class correlation coefficients (ICC) were also calculated to assess reproducibility; acceptable ICCs were defined as greater than or equal to 0.4.  The ICC values for the Stimpod ranged from 0.425 to 0.79, depending on pulse width, digit, and stimulation; ICCs for the Neurometer were 0.615 and 0.735 at 250 and 2,000 Hz, respectively.  These values were considered acceptable; however, the Neurometer performed less efficiently at 5-Hz (ICCs for the 2nd and 5th digits were 0.292 and 0.318, respectively).  The authors concluded that the Stimpod device displayed good to excellent reproducibility in measuring CPT in healthy volunteers, while the Neurometer displayed poor reproducibility at low frequency (5-Hz).  They stated that these findings suggested that peripheral nerve stimulators may be potential devices for measuring CPT to assess nerve blocks.

Cervicogenic Headaches / Cluster Headaches

Grandhi and colleagues (2018) noted that cervicogenic headache (CHA) is a secondary headache that has a source in the upper cervical spine.  Many traditional analgesic choices lack good efficacy in managing the associated pain.  As a result, in management of CHA, RFA or PRF has been tried with success.  These investigators examined the use of RFA and PRF for the management of CHA.  In the present investigation, a review of the literature was conducted using PubMed (1966 to February 2017).  The quality assessment was determined using The Cochrane Risk of Bias.  After initial search and consultation with experts, a total of 34 articles were identified for initial review and 10 articles met inclusion for review.  Criteria for inclusion were primarily based on identification of articles discussing CH, which were previously treatment-resistant and occurred without any other pathology of the craniofacial region or inciting event such as trauma.  This systematic review demonstrated that RFA and PRFA provided very limited benefit in the management of CHA.  At present, there is no high-quality RCT and/or strong non-RCTs to support the use of these techniques, despite numerous case reports that had demonstrated benefit.  The authors concluded that this review was one of the first to provide a comprehensive overview of the use of RFA and PRF in the management of CHA.

Lee and associates (2020a) stated that although conventional high-temperature C2 DRG RFA was effective in patients with cervicogenic headache (CEH) in previous studies, the effect of pulsed RFA on C2 DRG in cases of CEH has not yet been evaluated.  In a retrospective study, these researchers examined the effectiveness and complications of C2 DRG PRFA for CEH and identified factors related to the outcome of the procedure.  They examined the electronic medical records of consecutive patients who underwent C2 DRG block for CEH from January 2012 to May 2018 at a pain center.  Consequent C2 DRG PRFA was carried out for patients in whom the headache recurred after an initial period of relief 24 hours after the C2 DRG block. A  successful outcome was defined as at least 50 % pain relief at 6 months after C2 DRG PRFA.  These investigators also examined variables associated with the outcome and prognostic factors of CEH.  Fluoroscopy-guided C2 DRG block was performed in 114 patients with CEH; 45 patients received C2 DRG PRFA and 40.0 % among them (18/45, success group) had greater than or equal to 50 % pain relief after 6 months . There were no post-procedure complications throughout the study period.  Significantly more patients in the success group than in the failure group had a definite positive response (greater than or equal to 50 % pain relief) to a previous C2 DRG block (p < 0.001).  The authors concluded that C2 DRG PRFA may be an effective treatment for patients with CEH, especially for patients who have previously experienced definite pain reduction after C2 DRG block.  However, the limitations of this study’s design and small number of patients precluded firm conclusions.

Lazzari and colleagues (2020) stated that the management options for chronic cluster headache (CCH) are limited and a significant proportion of patients become refractory to pharmacotherapies.  Pulsed radiofrequency of the sphenopalatine ganglion (SPG) may present an effective, minimally invasive treatment modality for patients with refractory CCH.  Thee investigators described the clinical outcomes of 14 patients with refractory CCH treated with PRF of the SPG.  Patients with medically refractory CCH who underwent percutaneous SPG-PRF treatment between January 2016 and April 2019 were included in this study.  Patients obtaining at least 30 % reduction in weekly cluster attacks for at least 3 months were defined as responders; treatment-related side effects were collected.  A total of 14 patients were included in this report (9 male subjects).  At a median follow-up of 6.5 (range of 6 to 13) months post-procedure, 8 patients (57.1 %) were defined as responders to the treatment; 6 patients were non-responders and reported either a reduction in frequency and severity of attacks for less than 3 months (2/6), no improvement (2/6) or temporary worsening of symptoms (1/6).  The majority of patients (63.6 %, n = 7/11) treated with greater than 45 V were responders compared with responders treated with 45 V (33.3 %, n = 1/3); 5 patients (35.7 %) experienced post-procedural side effects.  The authors concluded that the findings of this this case-series study suggested that PRF targeting the SPG might offer a safe, minimally invasive and effective treatment for medically refractory CCH.  Moreover, these researchers stated that given the small number of cases and the short follow-up, larger and more robust studies are needed to confirm these findings.

Li and co-workers (2020) stated that chronic headache is common but difficult to treat.  Most patients respond poorly to drugs.  Nerve block is an effective treatment but has no continuous effect.  These researchers examined the long-term effectiveness of C2 DRG after PRF guided by US for the treatment of chronic headache.  A total of 20 patients who did not respond to medications and peripheral nerve blocks underwent US-guided PRF of the C2 DRG.  Patients were followed-up for 6 months; VAS score was evaluated at 1 week, 1 month, 3 months, and 6 months.  The QOL was assessed by Brief Pain Inventory (BPI) scores, which were rated at pre-procedure and 1 month, 3 months, and 6 months after the procedure.  The occurrence of complications was evaluated and reported.  Mean VAS scores were significantly decreased at 1 week, 1 month, 3 months and 6 months compared to the pre-procedure mean VAS score.  Mean BPI scores decreased significantly at each post-operative time-point compared to the pre-operative baseline and low scores remained throughout the follow-up period: 45.05 ± 3.44 at pre-procedure, 10.60 ± 2.37 at 1 weeks, 12.50 ± 2.46 at 1 month, 12.90 ± 2.62 at 3 months, and 11.63 ± 2.98 at 6 months.  Mild complications occurred, including 1 case (4.7 %) of transient cervicalgia (lasting for 24 hours) and 3 cases (14.2 %) of transient dizziness (lasting for 30 mins).  The authors concluded that C2 PRF may be considered as an alternative treatment for chronic headache.  They stated that limitations of this study included small sample size (n = 20), and the short duration of the follow-up (6 months).  Moreover, these researchers stated that further studies with larger samples of patients and a more extended observation period should be carried out to confirm the effectiveness of this new method.

Abdominal Cutaneous Nerve Entrapment Syndrome

Maatman and co-workers (2018) noted that chronic abdominal pain is occasionally due to entrapped intercostal nerve endings (ACNES, abdominal cutaneous nerve entrapment syndrome).  If abdominal wall infiltration using an anesthetic agent is unsuccessful, a neurectomy may be considered; PRF is a relatively new therapeutic option for various chronic pain syndromes.  Evidence regarding a beneficial effect of this minimally invasive technique in ACNES is lacking.  These investigators evaluated the effectiveness of PRF treatment in ACNES patients.  A series of ACNES patients undergoing PRF treatment between January 2014 and December 2015 in 2 hospitals were retrospectively evaluated.  Pain was recorded prior to treatment and after 6 weeks using NRS (0 (no pain) to 10 (worst possible pain)).  Successful treatment was defined as greater than 50 % NRS pain reduction.  Patient satisfaction was scored by patient global impression of change (PGIC, 1 = very much worse, to 7 = very much improved).  A total of 26 patients were studied (17 women, median age of 47 years, range of 18 to 67 years).  After 6 weeks, mean NRS score had dropped from 6.7 ± 1.2 to 3.8 ± 2.3 (p < 0.001).  A mean 4.9 ± 1.4 PGIC score was reported by then.  Short-term treatment success (6 to 8 weeks) was 50 % (n = 13, 95 % CI: 29 to 71), while 8 % was pain-free on the longer term (median of 15 months).  Median effect duration was 4 months (range of 2 to 26).  The authors concluded that PRF was temporarily effective in 50 % of patients with ACNES.  They stated that PRF was safe and may be favored in neuropathic pain syndromes as nerve tissue destruction was possibly limited.  These researchers stated that a RCT determining the potential additional role of PRF in the treatment strategy for ACNES is underway.

The authors stated that this study had several drawbacks including its retrospective character whereas a relatively small sample size (n = 26) limited its power and generalizability.  Furthermore, a control group eliminating the bias of the placebo effect of a novel treatment option or spontaneous resolution of symptoms was lacking.  A previous study showed that a placebo effect of invasive procedures was possibly higher compared to oral medication pills.  In addition, some authors suggested that improvement of symptoms that was not obtained in a blind manner was per definition caused by a placebo effect.  Therefore, a potential placebo effect could not be ruled out.  However, the results of this study on PRF in ACNES patients must be seen in the proper context.  It must be appreciated that most of these patients were referred after a median of over half a year of diagnostic delay suggesting that this pain syndrome is still frequently overlooked as a cause of chronic abdominal wall pain.  It is thus unlikely that the beneficial effect of PRF can be seen solely as placebo effect, since other therapies failed to achieve any success.  In addition, a randomized sham-controlled trial showed a beneficial effect for PRF against sham intervention.  It must be realized that this study represented the only case series on PRF in ACNES at present providing insight on a “proof of principle” regarding the efficacy of PRF.  However, an RCT that is currently underway will identify a possible placebo effect.

Chronic Perineal Pain

Usmani and colleagues (2018) noted that chronic non-oncological perineal pain has been effectively managed by ganglion Impar block.  Chemical neurolysis, cryoablation, and RFA have been the accepted methods of blockade.  Recently, PRF, a novel variant of conventional RF, has been used for this purpose.  In a prospective, randomized, double-blind study, these researchers compared the efficacy of conventional RF and PRF for ganglion Impar block.  Patients were randomly allocated to 1 of 2 groups.  In the conventional RF (CRF) group (n = 34), conventional RFA was performed, and in the PRF group (n = 31), PRF ablation was carried out.  After informed and written consent, fluoroscopy-guided ganglion Impar block was performed through the 1st intra-coccygeal approach.  The extent of pain relief was assessed by VAS at 24 hours, and at the 1st, 3ird, and 6th weeks following the intervention.  A questionnaire to evaluate subjective patient satisfaction was also used at each follow-up visit.  In the CRF group, the mean VAS score decreased significantly from the baseline value at each follow-up visit.  But in the PRF group, this decrease was non-significant except at 24-hour follow-up.  Inter-group comparison also showed significantly better pain relief in the CRF group as compared with the PRF group.  At the end of follow-up, 28 patients (82 %) in the CRF group and 4 patients (13 %) in the PRF group had excellent results, as assessed by the subjective patient satisfaction questionnaire.  There was no complication in any patient of either study group, except for short-lived infection at the site of skin puncture in a few.  The authors concluded that ganglion Impar block by conventional RF provided a significantly better quality of pain relief with no major side effects in patients with chronic non-oncological perineal pain as compared with PRF.  The authors stated that the short-term follow-up period of only 6 weeks was a major drawback associated with this study.

Glossopharyngeal Neuralgia

Bharti and associates (2018) stated that the management of glossopharyngeal neuralgia (GPN) due to oropharyngeal carcinoma is particularly difficult because of rich innervations of the area, erosive nature of neoplasm and dynamic pain evoked by the functional movements like swallowing and chewing.  Few case reports have shown the efficacy of PRF treatment in primary and secondary GPN in non-cancer patients.  However, the efficacy of PRF ablation of the glossopharyngeal nerve in oral cancer patients is unknown.  In a prospective interventional clinical trial, these researchers evaluated the safety and efficacy of PRF ablation of the glossopharyngeal nerve for the management of oropharyngeal cancer pain involving the base of the tongue, tonsillar fossa, and oropharynx.  A total of 25 adult patients suffering from oropharyngeal carcinoma complaining of severe pain in the area mainly supplied by the glossopharyngeal nerve were included.  Subhects underwent fluoroscopy-guided PRF ablation of the glossopharyngeal nerve of the affected site 3 times at 42°C temperature for 120 seconds with 22-G, 10-cm long, 5-mm active tip radiofrequency needle.  They were followed-up for 1 year for pain relief, nausea-vomiting and sleep disturbances.  The treatment was considered effective if there was 50 % reduction in pain score at 2 weeks.  There was significant reduction in the overall pain score including site specific pain, odynophagia and ear pain after RFA(p < 0.0001) in all the patients.  This was associated with decreased opioid consumption (p < 0.001), lesser nausea/vomiting, and improved sleep.  The treatment was effective in 23 out of 25 patients (92 %) for more than 3 months.  No major complication was observed in any patient.  The average duration of effective pain relief was 5 to 9 months.  The authors concluded that these findings showed that PRF ablation could be used safely and effectively for the treatment of GPN secondary to oropharyngeal carcinoma.  Moreover, these investigators noted that patients having bilateral GPN or an advanced stage of oral cancer with large lymph nodes at the angle of mandible were not included.  They stated that this study was a single-center, observational clinical trial and further multi-center, RCTs are needed to obtain higher level of evidence.

Han et al (2022) provided a comprehensive review of the most recent literature on glossopharyngeal neuralgia (GPN).  It covered the epidemiology, risk factors, pathophysiology, and differential diagnosis given that GPN can often be confused with other facial pain syndromes.  These investigators also reviewed recent findings regarding medical or conservative measures, minimally invasive, and surgical options for potentially treating and managing GPN.  An in-depth analysis of the recent literature indicated that GPN is not only rare, but its etiology and pathophysiology are complex and are often secondary to other disease processes.  Regardless, current therapeutic options are shown to be effective in controlling pain.  Conservatively, 1st-line management of GPN is carbamazepine, but gabapentin and eslicarbazepine acetate are suitable alternatives.  In terms of current minimally invasive pain management techniques, pulsed RFA, nerve blocks, or percutaneous RF thermocoagulation are effective.  Finally, surgical management entails micro-vascular decompression and rhizotomy.  The authors concluded that while there are currently many viable options for addressing GPN pain ranging from conservative to surgical management, further research is needed because GPN is such a rare disease process, and more effective approaches should be examined in the future.

Hemiplegic Shoulder Pain

Picelli and co-workers (2018) stated that hemiplegic shoulder pain (HSP) is the most common pain condition after stroke.  To-date, there is no study regarding the effects of PRF treatment for HSP.  These researchers reported on a case series about its use in chronic stroke.  A total of 6 chronic stroke patients with HSP (VAS score for pain greater than or equal to 30 mm) underwent US-guided supra-scapular nerve (SSN) PRF treatment.  All were evaluated before treatment and at 4 and 16 weeks of follow-up.  The main outcome was VAS score; secondary outcomes were modified Ashworth Scale, shoulder passive range of motion (PROM), Disability Assessment Scale (DAS), Fugl-Meyer Assessment, and EuroQol-5 dimension questionnaire (EuroQol-5D) scores.  As compared with baseline, improvement was observed in the following parameters: VAS for pain (at 4 weeks, p = 0.023; at 16 weeks, p = 0.023); shoulder PROM for abduction (at 4 weeks, p = 0.023; at 16 weeks, p = 0.024), flexion (at 4 and 16 weeks, p = 0.024), extension (at 4 and 16 weeks, p = 0.02), and external rotation (4 and 16 weeks, p = 0.02); DAS for hygiene (at 4 and 16 weeks, p = 0.024), dressing (at 4 weeks, p = 0.02; at 16 weeks, p = 0.024), and pain (at 4 weeks, p = 0.024; at 16 weeks, p = 0.023); and EuroQol-5D (at 4 and 16 weeks, p = 0.024).  The authors concluded that these findings supported the use of US-guided SSN PRF treatment for HSP in chronic stroke patients.  Moreover, they stated that future larger RCTs are needed to confirm these preliminary findings.

The authors stated that this study had several drawbacks.  First, it did not have a prospective design and the sample size was small (n = 6).  These researchers estimated that a total of 27 patients would provide 90 % power to detect a difference of 13 mm on the VAS (minimal clinically important difference) at the primary end-point.  Second, there was no control group treated with placebo or other treatments (e.g., intra-articular injection, local anesthesia, botulinum toxin, physical therapy) for shoulder pain.  Third, no further US evaluation of the SSN was done after PRF.  Thus, these investigators had no information about any SSN structural change or nerve echo signal modification following treatment.

Idiopathic Axonal Polyneuropathy

Lee and Chang (2018) stated that many patients with chronic idiopathic axonal polyneuropathy (CIAP) suffer from neuropathic pain, which is managed using several oral medications and modalities.  However, despite these treatments, pain persists in some patients.  In a prospective study, these investigators examined the effect of caudal epidural PRF for the management of CIAP-induced refractory neuropathic pain.  A total of 20 patients with neuropathic pain and a diagnosis of refractory CIAP were recruited.  For PRF stimulation, a 22-G cannula was inserted into the epidural space through the sacral hiatus under fluoroscopic guidance; PRF stimulation was administered once at 5-Hz with a 5-ms pulse width for 600 seconds at 55 V.  The effect of stimulation was evaluated using a NRS at 2 weeks and 1, 2, and 3 months after the procedure.  Successful pain relief was defined as a reduction in the NRS score of greater than or equal to 50 % as compared with the score prior to treatment.  In addition, at 3 months after treatment, patient satisfaction levels were examined; patients that reported "very good" (score = 7) or "good" (score = 6) results were considered to be satisfied with the procedure.  Neuropathic pain was significantly reduced at 2 weeks and at 1, 2, and 3 months follow-up after PRF (p < 0.001, repeated measures 1-factor analysis).  In addition, at 3 months post-PRF, 50 % of the patients achieved a successful response (greater than or equal to 50 % pain reduction) and were satisfied with treatment results.  The authors concluded that caudal epidural PRF may be a good therapeutic option for managing neuropathic pain induced by CIAP, especially when pain is unresponsive to oral medications.  The main drawbacks of this study were its small sample size (n = 20), and the lack of long-term follow-up evaluations.

Idiopathic Supraorbital Neuralgia

Luo and associates (2018) stated that no ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks.  The efficacy of percutaneous PRF for the treatment of refractory idiopathic supraorbital neuralgia is unclear.  These researchers evaluated the safety and efficacy PRF for the treatment of patients with refractory supraorbital neuralgia.  They prospectively examined the long-term effects of US-guided percutaneous PRF in the treatment of 22 refractory idiopathic supraorbital neuralgia patients.  A reduction in the verbal pain NRS score of more than 50 % was used as the standard of effectiveness.  The effectiveness rates at different time-points within 2 years were calculated.  After a single PRF treatment, the effectiveness rate at 1 and 3 months was 77 %, and the rates at 6 months, 1 year, and 2 years were 73 %, 64 %, and 50 %, respectively.  Except for a small portion of patients (23 %) who experienced mild upper eyelid ecchymosis that gradually disappeared after approximately 2 weeks, no obvious complications were observed.  The authors concluded that the findings of this study demonstrated that for patients with refractory idiopathic supraorbital neuralgia, percutaneous PRF may be a safe and effective treatment choice.  These preliminary findings need to be validated by well-designed studies.

Intercostobrachial Neuralgia in Post-Mastectomy Pain Syndrome

Fam and colleagues (2018) stated that breast cancer is a common neoplastic tumor in women, and the post-mastectomy pain syndrome (PMPS) has been reported frequently after surgical treatment.  The injury of the intercostobrachial nerve is considered the major cause of this type of pain.  These researches evaluated the safety and efficacy of PRF and steroid injection on the 2nd and 3rd thoracic (T2 and T3) dorsal root ganglions (DRGs) for inter-costo-brachial neuralgia (ICBN) post-mastectomy.  This study was conducted on 100 patients with ICBN post-mastectomy.  The PRF waves were applied for 120 seconds twice on T2 and T3 DRGs; then 1 ml of 4-mg dexamethasone and 1 ml of bupivacaine 0.25 % were injected at each level then the technique was repeated 3 times 1 week apart for each patient.  After 6 months from the latest intervention, the mean VAS dropped from 7.48 to 4.7 (p = 0.005712) and the mean of the QOL scale improved to 6.88 after being 4.66 (p < 0.00001) before the intervention and 64.68 % of the patients decided that they would certainly repeat the procedure if they could go back in time and 66.64 % would certainly recommend the same procedure to a family member.  The analgesics consumption decreased mainly in the 1st month but increased again after 6 months (non-significant).  No serious complications were recorded.  The authors concluded that PRF and steroid injection on T2 and T3 DRGs assumed a safe and effective method for ICBN post-mastectomy treatment.

The authors stated that this study had several drawbacks: First, despite the widely use of the PRF in the clinical practice for control of neuropathic pain, the ideal parameter of it is not well-determined unlike the thermal RF.  Second, limited number of patients and absent control group was another drawback, so further research with larger patient populations from multiple health centers is a must.  Lastly, the 6 months follow-up program might not have been enough time to detect the long-term effects of the PRF for neuropathic pain management.

Hetta and colleagues (2020) noted that pharmacologic treatment is not successful in all cases of PMPS.  Some patients continue suffering pain while taking their medications, and others could not tolerate the side effects of anti-neuropathic analgesics; RF technology has provided promising results in the management of chronic neuropathic pain.  In a prospective RCT, these researchers examined the effectiveness of PRF when delivered either on thoracic DRG of intercostobrachial nerves (thoracic DRG 2, 3, and 4) or their corresponding thoracic para-vertebral nerves (PVNs).  A total of 64 patients complaining of PMPS were randomized to either group DRG (n = 32) that received PRF on thoracic DRG, or group PVN (n = 32) that received PRF on thoracic PVN.  The outcome variables were that the patients showed greater than 50 % reduction in their VAS pain score; the VAS pain score and GPE was evaluated during a 6-month follow-up period.  The percentage of patients who showed greater than 50 % reduction of their VAS pain score was significantly higher in group DRG compared with group PVN, assessed at 4 and 6 months post-procedure (23/29:79.3 % versus 13/29:44.8 %; p = 0.007) and (22/29:75.9 % versus 7/29:24.1 %; p < 0.001), respectively, however, the 2 groups did not significantly differ at 1, 2, and 3 months post-procedure (DRG versus PVN), (21/29: 72.4 % versus 21/29: 72.4 %; p = 0.542), (24/29: 82.8 % versus 23/29: 79.9 %; p = 0.778), and (24/29: 82.8 % versus 19/29: 65.5 %; p = 0.136), respectively.  There was a statistically significant reduction of VAS pain score at 4 and 6 months (DRG versus PVN, mean ± SD, 2.9 ± 2 versus 3.9 ± 1.5; MD (95 % CI: 1 (0.06 to 1.9); p = 0.038; 3 ± 1.94 versus 5.1 ± 1.5; MD (95 % CI: 1.9 (1 to 2.9); p < 0.001, respectively), however, the 2 groups did not significantly differ at 1, 2, and 3 months post-procedure.  With regard to the patient's satisfaction (i.e., GPE), assessed at 3 and 6 months post-procedure, there was a significantly higher satisfaction in group DRG compared with group PVN (median [interquartile range (IQR)], 6 (5:7) versus 3 (2:4); p < 0.001), however, the patient's satisfaction was similar between groups at 3 months post-procedure: median (IQR), 6 (4:7) versus 6 (5:6); p = 0.327.   The authors concluded that PRF of both the thoracic DRG and the thoracic PVN were effective treatments for PMPS; however, PRF of DRG provided a better long-term analgesic effect.  Nevertheless, given the inherent risk of performing thoracic foraminal interventions and the technical difficulty of targeting thoracic DRG, these investigators recommended that PRF of DRG should be reserved for cases that failed to gain adequate response to PRF of thoracic PVN in conjunction with medical treatment.  They stated that future trials are needed to compare the analgesic effect of both techniques on diversity of thoracic pain syndromes and for an extended follow-up time period.

The authors stated that this study was limited by the relatively short post-procedure follow-up period (6 months).  Moreover, these researchers could not maintain a fixed analgesic protocol for all patients because of diversity of medications received by the patients prior to the intervention, such as amitriptyline, duloxetine, gabapentin, and tramadol.  Furthermore, some patients were receiving analgesics for another pain conditions such as metastatic bone pain, chemotherapy-induced neuropathy, and osteoarthritis.  In addition, these investigators did not inject any local steroids to ameliorate neuronal edema and subsequent post-operative soreness that could occur following PRF to be sure that the achieved analgesic effect was purely due to PRF.

Palmar Hyperhidrosis

Lin and co-workers (2017) noted that palmar hyperhidrosis (PH) exhibits excessive and unpredictable sweating.  The most effective treatment for permanent cure is the ablation of thoracic sympathetic ganglia innervating hands.  However, sympathectomy of T2 sympathetic ganglion by clipping or cauterization causes irreversible nerve damage, and results in a compensatory hyperhidrosis (CH).  In an animal study, these researchers employed PRF stimulation to reversibly block sympathetic ganglion to treat PH and avoid CH.  A bipolar electrode was implanted into the right T2 sympathetic trunk by endoscopic surgery and PRF was delivered through the electrode.  The humidity (%) of right palm was measured to indicate sweating level; 6 out of 13 rats (46.2 %) that received a 5-min PRF stimulation on the T2 sympathetic trunk showed a decrease in the right palm humidity during the surgery; PRF stimulation significantly reduced humidity from 69.17 % ± 0.72 % obtained from baseline condition to 66.93 % ± 0.69 %.  The humidity reduction was also observed at 10 mins after the PRF stimulation.  These investigators further evaluated the effect of PRF stimulation 1 week after surgery and found that the PRF stimuli reduced right hand humidity in 5 out of 8 rats (62.5 %); PRF stimulation significantly reduced humidity from 66.11 % ± 0.81 % obtained from sham operation control to 63.62 % ± 0.82 %.  The percentage of right hand humidity obtained 10 mins after PRF stimulation was also reduced to 63.38 % ± 0.80 %.  Anesthetics have no effect on humidity.  The authors concluded that these findings indicated that PRF stimulation of T2 sympathetic trunk reduced palm sweating in rats.  These preliminary findings need to be further investigated in human subjects.

Peripheral Neuralgia

Abd-Elsayed and associates (2018a) noted that peripheral nerve pain is common among patients with typical management including the use of pain medications, neuropathic agents, steroid injections, and nerve blocks.  Previous studies investigating the effectiveness of RFA and PRF, typically case reports, have demonstrated that peripheral nerve RFA and PRF have the potential to provide relief of chronic pain for long duration.  In a retrospective review, these researchers examined the efficacy of RFA/PRF in the treatment of peripheral neuralgia.  They identified 16 patients who received 17 RFAs/PRFs.  Outcomes of interest collected included pain scores before and after procedures, percent improvement in pain after each procedure, and duration of improvement until the time of data collection.  In addition, demographic data including age, sex, and nerves involved were collected.  A total of 11 patients (12 RFAs/PRFs) (80 %) reported improvement after their procedure.  Pain scores improved significantly from 6.3 ± 2.3 before each procedure to 3.6 ± 2.7 after each procedure (p = 0.003).  A total of 11 patients (12 RFAs/PRFs) reported an average improvement of 60.8 % ± 35 % after their procedure with an average duration of improvement of 128.8 ± 106.8 days.  The authors concluded that RFA and PRF can be used to treat chronic peripheral pain after conservative methods fail to do so.  Moreover, they stated that large clinical trials are needed to confirm these findings.

Peripheral Post-Traumatic Neuropathic Pain

In a double-blind, sham-controlled, randomized clinical trial, Akural and colleagues (2017) evaluated the safety and efficacy of PRF in the treatment of peripheral post-traumatic neuropathic pain (NP).  A total of 45 patients with peripheral post-traumatic NP in their upper or lower limb were randomly assigned to receive PRF or sham treatment to the injured peripheral nerve(s) causing peripheral post-traumatic NP.  Only patients whose pain intensity was at least 5 on NRS 0 to 10 and who had suffered from their NP for at least 6 months were included.  All patients had dynamic mechanical allodynia or pinprick hyperalgesia in their painful area.  They had achieved temporary pain relief of at least 50 % with a local nerve block performed at a previous visit.  The primary efficacy variable was the difference in 3-day mean pain intensity score from the baseline to 3 months.  Other variables included response defined as greater than or equal to 30 % reduction in mean pain intensity at 3 months compared to baseline, Neuropathic Pain Scale (NPS) results, health-related QOL (SF-36) and adverse effects.  The skin was anesthetized with 1 % lidocaine.  A RF needle was introduced through the skin, and then guided to a SMK cannula (52, 100 or 144 mm depending on the target nerve) with 4 or 5 mm active tip (SMK-C5-4, SMK-C10-5, SMK-C15-5, Radionics, Burlington, MA).  The nerve was located accurately by stimulating at 50 Hz (threshold less than 0.5 V).  Sham treatment or PRF was applied for 120 seconds 1 to 4 times at each treatment point (Radionics, Burlington, MA).  The total treatment time was up to 8 minutes.  Both patients and clinicians were blinded during the whole treatment and follow-up period.  A total of 43 patients were included in the analyses.  There was no statistically significant difference between PRF and sham treatment for the primary outcome efficacy variable; 7 patients (3 in PRF group and 4 in sham treatment group) achieved greater than or equal to 30 % pain relief (difference between groups was non-significant).  There was no statistically significant difference in the NPS or any dimension of SF-36 between the treatments; 18 patients reported adverse effects.  They were mild and did not necessitate any treatment.  Transient pain was reported by 17 patients, local irritation by 5 patients and local inflammation by 1 patient.  There was no significant difference between the groups in the presence of adverse effects.  The authors concluded that PRF was well-tolerated, but this study failed to show efficacy of PRF over sham treatment for peripheral post-traumatic NP.  Based on these findings, these investigators do not recommend PRF for peripheral post-traumatic NP.  They stated that more research of the possible use of PRF for various pain conditions is needed to determine its role in the management of prolonged pains.

Post-Surgical Orchialgia

Hetta and colleagues (2018) stated that chronic post-surgical pain in the groin region represents a challenge for the managing physician and is a burden on the QOL of the patient.  None of the existing interventions or medical treatment is satisfactory.  In a prospective, randomized, controlled clinical trial, these researchers evaluated the analgesic efficacy of PRF applied to the ilio-inguinal nerve and the genital branch of the genito-femoral nerve for patients suffering from chronic post-surgical orchialgia.  A total of 70 patients complaining of chronic post-surgical orchialgia were randomized into 2 groups: PRF group (n = 35), received PRF on the ilio-inguinal nerve and genital branch of the genito-femoral nerve, or sham group (n = 35).  The percentage of patients that showed greater than 50 % reduction of their VAS pain score as well as the percentage of patients that did not require additional analgesic drugs was assessed.  The VAS pain score and the global perceived effect (GPE) were reported during the 3-month follow-up period.  The percentage of patients who showed greater than 50 % reduction of their VAS pain score was 80 % (24/30) in the PRF group versus 23.33 % (7/30) in the sham group.  The percentage of patients that did not require analgesic drugs was 50 % (15/30) in the PRF group versus 3.3 % (1/30) in the sham group.  There was a significant reduction of the mean post-procedural VAS pain score at 2, 4, 6, 8, and 12 weeks (p = 0.001) in the PRF group in comparison to the sham group.  Likewise, there was a significant improvement of the GPE in the PRF group in comparison to the sham group (p = 0.00).  The authors concluded that for patients suffering from chronic post-surgical orchialgia, PRF applied to the ilio-inguinal nerve and the genital branch of the genito-femoral nerve was an effective treatment modality; it provided long-lasting pain relief and decreased the demand for pain medications.  The main drawbacks of this study were its short-term follow-up period (3 months) and its relative small sample size (n = 35 in the PRF group).  These preliminary findings need to be validated by well-designed studies.

Stump Pain

Zheng and co-workers (2017) stated that the post-amputation (pain) syndrome, including stump pain, phantom limb sensation, and phantom limb pain is common but difficult to treat.  Refractory stump pain is an extremely challenging and troublesome clinical condition.  Patients respond poorly to drugs, nerve blocks, spinal cord stimulation and surgery.  This report described a patient with persistent and refractory upper limb stump pain being successfully relieved with PRF of brachial plexus under US guidance after a 6-month follow-up period.  The authors concluded that the findings of this report suggested that PRF of brachial plexus under US guidance may be considered as an alternative treatment for refractory stump pain.  To the authors’ knowledge, this was the first report using US-guided brachial plexus PRF for the management of refractory stump pain.  These preliminary findings need to be validated by well-designed studies.

Ilfeld et al (2022) noted that post-amputation phantom and residual limb pain are common and frequently intractable, with few reliably effective treatments.  Pulsed nonthermal radiofrequency (RF) electromagnetic field (EMF) therapy is a non-invasive treatment used previously as an adjunct analgesic and wound healing therapy.  Its use for post-amputation pain remains unexamined.  In a case-series study, 12 patients with an above or below knee amputation with persistent, intractable phantom and/or residual limb pain unresponsive to multiple previous invasive treatments were provided with a non-invasive, wearable, pulsed EMF device (RecoveryRx, BioElectronics Corporation, Frederick, MD).  Patients used the included dressings to self-apply the 12 cm-diameter ringed antenna to their residual limb and then activated the device, which delivered nonthermal RF energy continuously for up to 30 days.  Of the 12 individuals, 4 (33 %) experienced minimal/no change, 7 (58 %) rated their phantom and/or residual limb pain as "very much improved" at the conclusion of treatment, and 1 (8 %) patient reported "moderate" improvement, using the Patient Global Impression of Change scale.  Of the 8 responders, worst and average phantom limb pain improved a mean (SD) of 4.0 (2.9) and 4.2 (1.8) points on the 0 to 10 numeric rating scale (NRS), respectively.  Worst and average residual limb pain improved 5.4 (3.7) and 3.5 (2.4) points, respectively.  The authors concluded that the findings from these cases suggested that pulsed EMF therapy may be an effective treatment for intractable post-amputation pain.  These investigators stated that considering the low patient burden of non-invasive, wearable devices, combined with few contraindications and no significant side effects or adverse events (AEs), further investigation with a RCT is needed.

Sural Neuralgia

Abd-Elsayed and associates (2018b) noted that sural neuralgia is persistent pain in the distribution of the sural nerve that provides sensation to the lateral posterior corner of the leg, lateral foot, and 5th toe.  Sural neuralgia is a rare condition but can be challenging to treat and can cause significant limitation.  These investigators presented 2 cases of sural neuralgia resistant to conservative management that were effectively treated by PRF ablation.  A 65-year old woman developed sural neuralgia after a foot surgery and failed conservative management.  She had successful sural nerve blocks, and PRF ablation led to an 80 % improvement in her pain.  A 33-year old woman presented with sural neuralgia secondary to 2 falls.  The patient had tried several conservative modalities with no success.  These researchers performed diagnostic blocks and PRF ablation, and the patient reported 80 % improvement in her pain.  The authors concluded that PRF ablation may be a safe and effective treatment for patients with sural neuralgia that did not respond to conservative therapy.  However, these investigators stated that studies are needed to elucidate its effectiveness and safety profile.

Plantar Fasciitis

Thapa and Ahuja (2014) stated that plantar fasciitis (PF) is the most common cause of chronic heel pain, which may be bilateral in 20 to 30 % of patients.  The management includes both pharmacological and operative procedures with no single proven effective treatment modality.  In the present case series, these investigators managed 3 patients with PF (1 with bilateral PF).  Following a diagnostic medial calcaneal nerve (MCN) block at its origin, these researchers observed reduction in verbal numerical rating scale (VNRS) in all 3 patients; 2 patients had relapse of PF pain that was managed with MCN block followed with PRF.  All the patients were pain-free at the time of reporting.  The authors concluded that this case series study highlighted the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.  These preliminary findings need to be validated by well-designed studies.

Li and colleagues (2018) stated that PF is one of the most common causes of adult heel pain.  These researchers compared the effectiveness of various therapies for PF using network meta-analysis.  Studies were searched on Embase, Medline via PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) up to December 4, 2017; RCTs that used extracorporeal shock wave therapy (ESWT), ultrasound (US), US-guided pulsed radiofrequency treatment (UG-PRF), intracorporeal pneumatic shock therapy (IPST), low-level laser therapy (LLLT), and non-invasive interactive neurostimulation (NIN) for the treatment of plantar fasciitis were included.  The primary outcome was change in pain relief.  Risk of bias was assessed using the Cochrane risk of bias tool. Quality assessment was performed using the GRADE system.  A total of 19 trials with 1,676 patients with PF were included.  In the pair-wise meta-analysis, radial extracorporeal shock wave therapy (RSW), LLLT, and IPST showed a significant pooled reduction in the VAS compared with placebo at 0 to 6 weeks [mean difference (MD) = 6.60, 95 % CI: 6.04 to 7.16; MD = 2.34, 95 % CI: 1.60 to 3.08; MD = 2.24, 95 % CI: 1.44 to 3.04, respectively].  Compared with placebo, UG-PRF [MD = 2.31, 95 % CI: 1.26 to 3.36] and high-intensity focused extracorporeal shock wave (H-FSW) [MD = 0.82, 95 % CI: 0.20 to 1.45] showed superior pain-relieving effects at 2 to 4 months; UG-PRF [MD = 1.11, 95 % CI: 0.07 to 2.15] and IPST [MD = 4.92, 95 % CI: 4.11 to 5.73] showed superior effects at 6 to 12 months.  In the network meta-analysis, only RSW induced significant pain reduction compared with placebo at 0 to 6 weeks [MD = 3.67, 95 % CI: 0.31 to 6.9].  No significant differences were found for the 2 to 4-month and 6 to 12-month periods because of the wide 95 % CIs.  The authors concluded that the present meta-analysis compared the effectiveness of 8 modalities for treating PF.  Regarding the 3 follow-up effectiveness time-points, RSW provided relatively more effective and stable pain relief compared with other interventions and is therefore a promising candidate for clinical applications.  Ultrasound therapy and FSW therapies could also be considered treatment candidates.  However, H-FSW and UG-PRF are not recommended.  Regarding the 0- to 6-week and 6- to 12-month periods, NIN and IPST provided the greatest pain relief, respectively, and, thus, have the potential to be more effective alternatives.  These researchers stated that randomized trials comparing NIN, IPST, UG-PRF, and LLLT are needed to obtain more precise estimates of their relative efficacy.

Complex Regional Pain Syndrome

Park and colleagues (2019) stated that PRF to the thoracic sympathetic ganglion (TSG-PRF) or to the cervical sympathetic chain (CSC-PRF) can be performed to overcome transient effects of single sympathetic blocks in patients with upper-extremity complex regional pain syndrome (CRPS).  These investigators retrospectively compared the clinical effects of TSG-PRF and CSC- PRF.  A total of 7 TSG-PRF cases and 10 CSC-PRF cases were enrolled in the present analysis.  These researchers examined effectiveness with multiple clinical measurements: a NRS of pain before and 1 week after the procedure, post-procedure temperature, effect duration, and a self-described patient satisfaction score.  The temperature was significantly higher in TSG-PRF cases than in CSC-PRF cases.  Pain values (according to the NRS) 1 week after the procedure were significantly lower, and the effect duration was significantly longer, after TSG-PRF than after CSC-PRF.  The authors concluded that TSG-PRF was a more effective procedure than CSC-PRF for managing chronic upper-extremity CRPS.  They stated that based on these preliminary findings, a well-designed, prospective study with adequate sample size would be a valuable advancement of this work.

The authors stated that this study had several limitations.  This analysis was not based on proper sample size due to retrospective nature.  In addition, although all patients reported various degrees of reduction in cold sensation after PRF, these researchers did not perform a diagnostic method to verify this objectively.  Along with a small sample size (n = 17), this was another limitation of the retrospective nature of this study.

Pudendal Neuralgia

Pudendal neuralgia (PN) involves severe, sharp pain along the course of the pudendal nerve, often aggravated with sitting.  The ideal management for PN has not been determined.  Rhame and colleagues (2009) presented a case of a female with 1.5 years of sharp, burning pain of the left gluteal and perineal regions.  She could not sit for longer than 10 to 15 mins.  Sacroiliac joint, epidural, and piriformis injections did not improve her pain.  She had tried acupuncture, massage, occupational therapy, and physical therapy but the pain persisted.  Medication treatment with amitriptyline, gabapentin, extended release morphine sulfate, and oxycodone-acetaminophen provided only minor relief and she had failed other multi-analgesic therapy.  She had been unable to work at her desk job for over 1 year.  She had a positive response to 2 diagnostic pudendal nerve blocks with lidocaine that provided pain relief for several hours.  This patient elected to undergo PRF of the left pudendal nerve in hopes of achieving a longer duration and improved pain relief.  Pulsed RF was performed at a frequency of 2 Hz and a pulse width of 20 milliseconds for a duration of 120 seconds at 42 degrees Celsius.  After the procedure, she reported tolerating sitting for 4 to 5 hrs.  Her multi-analgesic therapy was successfully weaned.  At 5 months follow-up, she felt motivated to return to work.  One and a half years after the procedure the patient is only taking oxycodone-acetaminophen for pain relief and still has good sitting tolerance.  There were no procedure-related complications.  To the authors'r knowledge PRF for the treatment of PN has not been reported elsewhere in the literature.  It is a relatively new procedure and is felt to be safer than continuous RF.  Current literature suggests that PRF delivers an electromagnetic field, which modifies neuro-cellular function with minimal cellular destruction.  The authors concluded that PRF of the pudendal nerve offers promise as a potential treatment of PN that is refractory to conservative therapy.

Frank and associates (2019) noted that PN is a recognized cause of chronic pelvic pain.  The diagnosis is complex, and there is no consensus on ideal management.  Many current methods do not provide adequate relief; PRF is a minimally invasive option that has been reported for its use in other neuropathies.  These researchers examined the feasibility and safety of using transvaginal PRF for the treatment of PN and generated a hypothesis on its efficacy.  They carried out a retrospective review of women who were treated with PRF for chronic pelvic pain owing to PN between January 2012 and December 2017 at an academic tertiary care center (Canadian Task Force Classification II-3).  A total of 7 patients were included.  The mean age was 43.7 (SD 7.97) years.  The average number of PRF treatments was 4.43 (range of 1 to 12), and the duration of effect averaged 11.4 weeks (SD 3.09).  There were no major or minor complications at the time of procedure or at follow-up visits.  The authors concluded that PRF may be a safe and effective therapeutic option for the management of PN for women in whom conservative management has not been effective.  Moreover, these researchers stated that future controlled studies are needed to confirm this hypothesis.

Peripheral Neuropathic Pain / Non-Neuropathic Pain

Chang (2018) noted that clinicians have recently been applying PRF stimulation on various peripheral nerves to manage patients' peripheral neuropathic pain.  This investigator reviewed the literature on the use and efficacy of PRF for controlling peripheral neuropathic pain.  This was a narrative review of relevant articles on the effectiveness of PRF for peripheral neuropathic pain.  A PubMed search was conducted for studies published from January 1, 1980 to August 31, 2017 that used PRF to treat peripheral neuropathic pain.  The key search phrase for identifying potentially relevant articles was [PRF and pain].  The following inclusion criteria were applied for the selection of articles: patients' pain was caused by peripheral nervous system disorders; PRF stimulation was applied on the peripheral nerve; and after PRF stimulation, follow-up evaluation was performed to assess the reduction in pain.  Review articles were excluded.  A total of 468 articles were found to be potentially relevant.  After reading the titles and abstracts of the papers and assessing them for eligibility based on the full-text articles, 63 publications were finally included in this review.  For trigeminal neuralgia, the results of previous studies indicated that PRF is not appropriate for managing trigeminal neuralgia and less effective than conventional RF.  Moreover, data on the use of PRF for PN, meralgia paresthetica, carpal tunnel syndrome, tarsal tunnel syndrome, and Morton's neuroma, is lacking and thus the efficacy of PRF in these peripheral nerve disorders cannot be determined at this time.

In a systematic review, Vuka and associates (2020a) examined the evidence on the safety and effectiveness of DRG-targeted PRF versus any comparator for treatment of non-neuropathic pain.  These investigators searched Medline, CINAHL, Embase, PsycINFO, clinicaltrials.gov and World Health Organization (WHO) clinical trial register until January 8, 2019.  All study designs were eligible; 2 authors independently conducted literature screening.  Primary outcomes were pain intensity and serious AEs (SAEs); secondary outcomes were any other pain-related outcome and any other safety outcome that was reported.  They evaluated the risk of bias using the Cochrane tool and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I); and conducted narrative evidence synthesis and assessed the conclusiveness of included studies regarding safety and effectiveness.  These researchers included 17 studies with 599 participants, which analyzed various pain syndromes.  Two studies were RCTs; both included participants with LBP.  Non-randomized studies included patients with the following indications: LBP, post-surgical pain, pain associated with herpes zoster, cervicogenic headache, CRPS type 1, intractable vertebral metastatic pain, chronic scrotal and inguinal pain, occipital radiating pain in rheumatoid arthritis and chronic migraine.  In these studies, the PRF was usually initiated after other treatments have failed.  A total of 11 studies had positive conclusive statements (11/17) regarding effectiveness; the remaining had positive inconclusive statements.  Only 3 studies provided conclusiveness of evidence statements regarding safety -- 2 indicated that the evidence was positive conclusive, and 1 positive inconclusive.  The risk of bias was predominantly unclear in randomized and serious in non-randomized studies.  The authors concluded that even though PRF of DRG was primarily studied for neuropathic pain, they had found as many as 17 published studies that have reported the use of DRG-targeted PRF in non-neuropathic pain conditions.  Although all of these studies reported positive information regarding the analyzed interventions, considerable caution is needed when interpreting these results as anything more than preliminary.  The quality of evidence was low, as there were only 2 RCTs among included studies, and the risk of bias was predominantly unclear in RCTs and severe among non-randomized studies.  The majority of studies included patients that had failed other therapies so these results could not be generalized.  These researchers stated that PRF treatment needs to be tested in high-quality and large-scale comparative studies, to confirm the effectiveness of this intervention.

In a systematic review, Vuka and colleagues (2020b) examined evidence regarding the safety and effectiveness of PRF applied to the DRG for the treatment of neuropathic pain.  These investigators searched Medline, CINAHL, Embase, and PsycINFO through January 8, 2019, as well as ClinicalTrials.gov and the clinical trial register of the WHO; all study designs were eligible.  They evaluated risk of bias using the Cochrane tool for RCTs and the ROBINS-I, and assessed level of evidence using the Oxford tool and quality of evidence with GRADE.  These researchers included 28 studies with subjects suffering from lumbo-sacral, cervical, or thoracic radicular pain, PHN, neuropathic bone pain in cancer patients, or carpal tunnel syndrome (CTS).  Only 5 studies were RCTs (RCTs), while others were of non-randomized designs, predominantly before and after comparisons.  A total of 991 subjects were included, with a median number (range) of 31 (1 to 101) subjects.  Only 204 subjects were included in the RCTs, with a median number (range) of 38 (23 to 62) subjects.  The overall quality of evidence was low, as the majority of the included studies were rated as evidence level IV or V; and the quality of evidence was very low.  The authors concluded that evidence regarding the safety and efficacy of PRF of the DRG for the treatment of neuropathic pain was based mainly on results from very small studies with low evidence quality.  Current findings about the benefits of PRF of the DRG for the treatment of neuropathic pain should be considered preliminary and confirmed in high-quality RCTs with sufficient numbers of subjects.

Chronic Knee Pain / Knee Osteoarthritis

Erdem and Sir (2019) stated that PRF of genicular nerves in the management of osteoarthritis (OA) related chronic knee pain has recently become a promising treatment.  Ultrasonography has replaced fluoroscopic guidance in pain medicine.  In a retrospective study, these investigators examined the effect of US-guided genicular PRF on knee pain and function in patients who had severe knee OA or who had previous knee arthroplasty.  This trial included a total of 23 patients with chronic knee pain, of which 17 patients were included in Group I (non-operated), and 6 patients were included in Group II (post-total knee arthroplasty [TKA]).  Treatment was based on US-guided PRF of the superior medial, superior lateral, and inferior medial genicular nerves.  The VAS and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores were evaluated before treatment, and at 3 weeks and at 3 months following the procedure.  Pulsed radiofrequency of the genicular nerves significantly reduced perceived pain and disability in the majority of the patients.  The proportion of the patients with improvement of greater than or equal to 50 % in pre-treatment VAS scores at 3 weeks and 3 months following treatment were 14 out of 17 patients (82 %) and 15 out of 17 patients (88 %) in Group 1, and 4 out of 6 patients (67 %), 4 out of 6 patients (67 %) in Group 2, respectively.  The authors concluded that the findings of this study suggested that US-guided PRF of genicular nerves was a safe and minimally invasive procedure that significantly alleviated pain and disability in patients with severe degenerative disease or with previous knee arthroplasty.

The authors stated that this study had several drawbacks.  First, the exact pathological processes of the OA and the source of the pain after TKA still remains uncertain.  The origin of the pain in the OA group (Group I) was suspected to be deformation of healthy bones, peri-articular tissues, and secondary synovitis.  However, in TKA group (Group II), mal-alignment of the implants, gap-balancing problems, inflammation, and remaining osteophytes may be considered.  Also, additional innervations apart from the genicular nerves exist that might cause continuation of pain transmission.  Consequently, the RF procedure including other nerves may result in different outcomes.  Second, the current study included a relatively small number of patients with TKA (n = 6); thus, the results could not be generalized to an overall population with TKA, and comparing non-operated and operated groups with an inequality in number distribution may not be strong supportive evidence.  However, these investigators observed that in the post-arthroplasty group, defining the neurovascular bundle was somewhat difficult due to the operation-related damages.  Despite a higher number of patients with pain after arthroplasty, these researchers performed the procedure only when the neurovascular bundle was identified clearly with US.  This may be the explanation of the small sample size in this study.  Third, the current study lacked a control group and thee researchers were unable to compare treatment with other modalities.  Finally, a 3-month follow-up period might not have been a sufficient length of time to evaluate the long-term results of the procedure.  Although the short-term follow-up data were superior, consistent with the literature, further studies are needed to evaluate the long-term effects of US-guided PRF genicular nerve treatment both in OA and post-arthroplasty cases.

Hong and colleagues (2020) stated that RF treatment is an invasive and promising procedure in the treatment of OA.  These investigators carried out a meta-analysis based on 12 RCT to examine if invasive RF treatment is more effective in relieving knee pain and improving knee function.  Relevant studies were searched on data-base of PubMed, Embase, EBSCO, Cochrane library, Wanfang digital database, VIP data-base, and CNKI up to January 2018.  A total of 841 participants from 12 publications were included.  The weighted mean difference (WMD) and the corresponding 95 % CIs were used to assess the difference in pain scores and OKS/WOMAC scores between RF treatment and control groups.  The statistical analysis was performed by Stata 12.0.  The pain scores (VAS) in the RF group were lower than those in the conservative treatment group after 1 week (WMD -1.77, 95 % CI: -2.93 to -0.61, p < 0.01), 1 month (WMD -1.40, 95 % CI: -1.98 to -0.82, p < 0.01), and 3 months (WMD -1.32, 95 % CI: -2.27 to -0.37, p < 0.01) of treatment, while there was no significant improvement in knee function.  In subgroup analyses by site of radiofrequency, RF mode showed some discrepancies in the WMD of VAS between the treatment and control groups.  In addition, subgroup analysis and meta-regression showed that the efficacy of RF treatment for reducing pain was reversely related to female ratio, and these researchers did not find any surgery-related adverse reactions.  The authors concluded that RF treatment significantly reduced the knee pain, but rarely improved the knee joint function; it had better efficacy than PRF ablation in reducing pain.  Furthermore, subgroup analysis and meta-regression suggested that women were more sensitive to RF treatment than men.  Moreover, they stated that due to the limitations of included literatures, the authenticity of the results requires further verification by prospective, multi-center RCTs.

The authors stated that this study had several drawbacks.  First, the WMDs of all combined trials showed a statistically significant reduction in VAS scores at some time-points, however, this difference was below the widely accepted, minimally clinically significant decrease in VAS of at least 2/10.  Second, the blind method was adopted in only 3 studies, indicating a potential high risk of bias.  This might be because blindness was not applicable in some studies.  Third, few or no data were related to cartilage mechanism or change in morphology.  In addition, only 1 RCT of cooled RF was included in this analysis.  The comparability of this treatment with other types of RF treatment needs further investigation.

In a systematic review and meta-analysis, Wu et al (2022) evaluated various RFA treatments for the treatment of knee OA and determined the best modality, target, number of electrodes, and image guidance for improving knee pain and function.  These investigators searched electronic databases for RCTs that compared the effectiveness of RFA treatments for knee OA from inception up to September 30, 2021.  The primary outcome was the VAS, and the secondary outcome was the WOMAC.  Bayesian network meta-analysis was carried out to synthesize the MD and rank the comparative effectiveness of treatments.  A total of 21 eligible RCTs (from 2011 to 2021, entailing 1,818 patients) with 8 RFA treatments, 6 IA injections, NSAIDS, exercise, and placebo were assessed.  Conventional bipolar genicular nerve RFA (GNRFA) had the greatest net benefit on the VAS at 6 months (MD, -5.5; 95 % CI: -4.3 to -6.7; SUCRA, 0.98), while cooled monopolar GNRFA had the greatest net benefit on the WOMAC at 6 months (MD, -33; 95 % CI: -37 to -29; SUCRA, 0.99).  In conventional and pulsed modalities, bipolar RFA was associated with a significant decrease in VAS and WOMAC than monopolar RFA.  Combining pulsed IA RFA and platelet-rich plasma (PRP) injection had no additional positive effects on VAS or WOMAC at 3 months.  The authors concluded that RFA was effective in improving both knee pain and function in patients with OA, at least in the short-term (6 months).  Patients responded better to the cooled modality than the conventional and pulsed modalities.  Bipolar was more effective than monopolar for improving pain and function in conventional and pulsed modalities.  Fluoroscopy and US guidance showed no differences in improving pain and function.  Moreover, these researchers stated that the effectiveness of RFA in cooled modality using bipolar or in combination with various IA injections remains to be compared.  

Frozen Shoulder

In a randomized, double-blind, sham control trial, Yan and  Zhang (2019) examined the safety and effectiveness of US-guided PRF (UG-PRF) for patients with frozen shoulder (FS).  A total of 136 patients with FS were recruited and then were equally randomly allocated into a treatment group (n = 68) and a sham group (n = 68).  Subjects in the treatment group received UG-PRF, while subjects in the sham group underwent sham UG-PRF.   Subjects in both groups were treated for a total of 12 weeks.  The primary outcome was the pain intensity, measured by the VAS.  The secondary outcomes consisted of shoulder disorder, measured by the score of shoulder pain and disability index (SPADI); QOL, assessed by SF-36; and any adverse events (AEs) during the treatment period.  All outcomes were measured at baseline, at the end of 6-week, and 12-week treatment.  At the end of 6 weeks, and 12 weeks, UG-PRF showed more promising outcome results in pain relief, as measured by VAS (p < 0.01), improvement of shoulder disorder, as assessed by SPADI score (pain, p < 0.01; disability, p < 0.01; total, p < 0.01), and enhancement of QOL, as measured by the SF-36 scale (PCS, p < 0.01; MCS, p < 0.01), compared with sham UG-PRF in this study.  The authors concluded that the findings of this study showed that UG-PRF may benefit for patients with FS after 12 weeks treatment.

The authors stated that this study had 2 limitations.  First, it did not include follow-up assessment following the treatment quit.  Therefore, further studies should extend the outcome evaluation period with follow-up visit after the treatment.  Second, since this study was the first study to examine the effectiveness of UG-PRF for FS, thus, more studies should be focused on this issue to further validate the findings of this study.

Infraorbital Neuralgia

Jia and colleagues (2019) stated that infraorbital neuralgia lacks systematic treatment guidelines because few studies on this subject have been published.  These investigators previously found that 42°C percutaneous non-destructive PRF treatment could achieve satisfactory pain relief for patients with infraorbital neuralgia.  However, patients who responded poorly to PRF had no other therapeutic options until now.  Recently, standard PRF combined with 60°C continuous radiofrequency (CRF) was successfully performed on trigeminal neuralgia patients and achieved a promising effective rate with mild complications.  However, the efficacy of the combined therapy in the treatment of infraorbital neuralgia has not yet been reported.  In a prospective, single-center, observational clinical trial, these researchers examined the effectiveness and safety of 42°C PRF combined with 60°C CRF in infraorbital neuralgia patients who responded poorly to 42°C PRF and were reluctant to receive destructive therapies or nerve decompression surgery.  These investigators examined the effects of 10 mins of 3-dimensional computer tomography (3D-CT)-guided 42°C PRF combined with 270 seconds of 60°C CRF in the treatment of 28 patients with refractory infraorbital neuralgia.  The response criterion was a post-operative verbal pain NRS score reduction of greater than 50 %.  The response rates at different time-points during a 2-year follow-up were calculated.  The effective rates of combined PRF and CRF treatment were 95.5 %, 86.4 %, 81.8 %, 72.7 %, 72.7 %, and 72.7 % post-operative at 1 month, 3 months, 6 months, 1 year, 18 months, and 2 years, respectively.  Except for 16 patients (72.7 %) experiencing mild numbness that gradually disappeared within 1 week to 2 months after the operation, no obvious complications were observed.  The authors concluded that for patients with intractable infraorbital neuralgia, 42°C PRF combined with 60°C CRF was a safe and effective treatment.  Moreover, these researchers stated that prospective, double-blind RCTs with longer follow-up periods are needed to examine if the combined treatment could become an alternative option for those who do not respond to conservative treatment, sparing those patients from destructive therapies or more invasive nerve decompression surgery. 

This study had several drawbacks.  First, the study evaluated the effectiveness and safety of combined 42°C PRF and 60°C CRF for only 2 years after the operation, a longer follow-up duration is needed to examine the long-term outcome of the novel combined therapy.  Second, the study recorded only the subjectively reported degree of facial numbness and did not include quantitative sensory testing to examine the degree of destruction by the operation.  Third, the cost of 3D-CT scanning was comparatively high, and patients were inevitably exposed to radiation energy, which would restrict clinical access.  Ultrasound appeared to be a safer and more economical imaging modality with which to guide the operation in future research.  Fourth, parameters measuring the effectiveness of the procedure, such as the treatment duration, waveform, pulse width, and frequency, need to be further studied.  Finally, this study was an observational, single-center study with small sample sizes (n = 28); multi-center, double-blind, RCTs with larger sample sizes are needed to provide a higher level of evidence of the efficacy of PRF combined with CRF.

Metatarsalgia

Ho and colleagues (2018) stated that metatarsalgia is characterized by pain in the forefoot, which is associated with increased stress over the metatarsal head region.  Despite the availability of a variety of conservative or surgical treatments for this condition, a few cases have demonstrated relapse or poor response to treatment.  Pulsed radiofrequency can provide pain relief in patients with diverse chronic conditions without causing neural injury.  Recently, studies have shown that US-guided PRF may be beneficial for adhesive capsulitis, carpal tunnel syndrome, tarsal tunnel syndrome, and recalcitrant plantar fasciitis.  These researchers described a successful case of significant pain relief achieved by using US-guided PRF targeting the posterior tibial nerve (PTN) at the ankle of a 67-year old woman with recalcitrant metatarsalgia.  Ten minutes after US-guided PRF was applied at the PTN, the patient reported decreased pain (from 8 to 3 on a VAS) and did not exhibit any particular side effects.  Three months after PRF application, the patient's VAS score remained more than 50 % below the baseline, and she did not need additional conservative treatment during the follow-up period.  The authors concluded that to the best of their knowledge, they presented the 1st case report using US-guided PRF at the PTN for treatment of recalcitrant metatarsalgia.  They hypothesized that US-guided PRF at the PTN may be a potentially novel approach for treating recalcitrant metatarsalgia.

Cervical Radicular Pain

Lee and colleagues (2020b) noted that the effect of PRF stimulation for alleviating cervical radicular pain has been demonstrated in several previous studies.  In a prospective, single-center study, these researchers examined the effectiveness of PRF with ultrasound (US) guidance in patients with chronic cervical radicular pain that was refractory to repeated transforaminal epidural steroid injections (TFESIs).  This trial included 49 patients with chronic cervical radicular pain, unresponsive to repeated TFESIs, and who underwent PRF stimulation under US guidance.  Using US, a cannula was inserted toward the cervical spinal nerve.  The pain intensity was evaluated using the NRS-11 for cervical radicular pain at pre-treatment and 1, 3, and 6 months post-treatment; and the Neck Disability Index (NDI) was used for evaluating functional disability before treatment and 6 months post-treatment.  Successful pain relief was defined as greater than or equal to 50 % reduction in the NRS-11 score as compared with the score before treatment.  Cervical radicular pain was significantly reduced at 1, 3, and 6 months post-PRF (p < 0.001).  At 6 months post-PRF, functional disability (NDI score) had significantly reduced, and 63.3 % of the patients achieved successful pain relief.  The authors concluded that PRF stimulation under US guidance is a potentially effective treatment for managing refractory chronic cervical radicular pain.  These researchers stated that the limitations of this study were the small sample size and the lack of long-term follow-up.  They stated that further studies  that address these limitations are needed.

Yang and Chang (2020) examined the effect of bipolar PRF in patients with chronic cervical radicular pain who were refractory to monopolar PRF and TFESI.  A total of 20 patients with chronic cervical radicular pain who were unresponsive to monopolar PRF and TFESI were included and underwent bipolar PRF of their cervical DRG.  Treatment outcomes were evaluated using the NRS for cervical radicular pain before treatment and 1, 2, and 3 months post-treatment.  Successful pain relief was defined as greater than or equal to 50 % reduction in the NRS score compared with the score before treatment.  Furthermore, at 3 months post-treatment, patient satisfaction levels were evaluated; those with very good (score =7) or good (score =6) results were considered to be satisfied with the bipolar PRF procedure.  Cervical radicular pain was significantly reduced at 1, 2, and 3 months post-PRF (p < 0.001).  In addition, at 3 months post-PRF, 50 % of the patients achieved a successful response and were satisfied with the treatment results.  The authors concluded that bipolar PRF on cervical DRG may be a good therapeutic option for managing refractory chronic cervical radicular pain. 

The authors stated that this study had several drawbacks.  First, this study was performed without a control group.  Second, the number of recruited patients was relatively small (n = 20).  Third, the long-term effects of bipolar PRF were not evaluated.  Lastly, these researchers could not clearly explain why bipolar PRF demonstrated a better treatment outcome than monopolar PRF.  They stated that further studies that address these limitations are needed.

Cervicogenic Headache

Park and colleagues (2021) stated that cervicogenic headache has been known to originate from the convergence of the upper 3 cervical and trigeminal afferents.  The administration of conservative treatments, interventional procedures, and more recently, PRF, has been used to relieve cervicogenic headache.  These researchers examined the safety and efficacy of PRF targeting the mid-cervical medial branches.  From September 2012 until December 2017, a total of 395 patients were diagnosed with cervicogenic headache based on the 3rd edition of the International Classification of Headache Disorders.  These investigators treated them conservatively at first, and those patients with non-resolution of pain were treated with mid-cervical medial branches block applied from C3 to C5 twice.  Subsequently, if any patient continued to experience persistent pain, these researchers classified them as having intractable cervicogenic headache and carried out PRF treatment targeting the mid-cervical medial branches from C3 to C5 bilaterally.  They analyzed their demographics and used a VAS to evaluate their pain for 12 months.  A total of 57 patients were enrolled in this study.  The mean age was 49.8 years, and the mean duration of symptoms was 47.7 months.  The mean VAS score was 6.21 before PRF treatment, and it improved to 1.54 immediately after the procedure without the symptoms recurring for a minimum of 12 months.  There were no severe complications, such as vascular or nerve injuries.  The authors suggested that PRF targeting the mid-cervical medial branches could be an alternative modality for patients with intractable CHA.  These investigators stated that randomized, controlled studies with a larger study sample are needed to examine the clinical effects of PRF targeting the mid-cervical medial branches.

The authors stated that this study had several drawbacks.  These researchers only examined the clinical outcome using a pain VAS.  Additional indices that evaluate the influence of cervicogenic headache on the patients’ QOL are needed.  This trial was a retrospective study and not a randomized controlled study.  To the authors’ knowledge, this study had the largest sample size among the published articles that analyzed PRF targeting the mid-cervical medial branches; however, the sample size was small (n = 57). 

Chronic Lumbosacral Radicular Pain

In a prospective, randomized study, Abdelrahman and colleagues (2021) examined the effect of using alpha lipoic acid (ALA) as an adjuvant therapy with PRF for the treatment of chronic lumbosacral radicular pain caused by herniated disc.  A total of 120 patients with lumbo-sacral radicular pain were randomized into 2 groups. Group I: treated with PRF at 42° C for 120 seconds.  Group II: treated as in group I, plus oral ALA 600 mg thrice-daily (1,800 mg/day) for 3 weeks then 600 mg once-daily for 2 weeks.  The lumbo-sacral radicular pain evaluated using the NRS and Oswestry Disability Index (ODI).  Success rate was significantly higher in group II at 3 and 6 months after intervention.  The median values of the NRS and the ODI were significantly lower in group II with no significant difference in Epworth Sleepiness Scale (ESS).  No major complications were reported in both groups.  The authors concluded that the findings of this study supported the adjunctive use of ALA with PRF on the dorsal root ganglion in the treatment of lumbosacral radicular pain.  These researchers postulated that oral supplementation of ALA aided in reducing progression of the nerve pathology via its anti-inflammatory action in the affected nerve.  The authors stated that this study had several drawbacks.  First, because the objective of the study was to provide evidence of the benefit of ALA as adjuvant therapy with no placebo medication used, subjects and medical personnel were not blinded.  Short-term period of the study was another drawback and these investigators recommended further studies with follow-up period up to 12 months.  Moreover, the effectiveness of PRF for the treatment of chronic lumbosacral radicular pain was confounded by the combined use of ALA.

Intercostal Neuralgia After Lung Cancer Surgery

In a retrospective, observational study, Wei and colleagues (2021) examined the effect of US-guided PRF (UGPRF) on intercostal neuralgia (ICN) after lung cancer surgery (LCS). This trial analyzed the outcome data of UGPRF on ICN in 80 patients with LCS.  All subjects were allocated into a treatment group (n = 40) and a control group (n = 40).  All patient data were collected between January 2018 and November 2019.  The primary outcome was pain intensity (measured by NRS).  The secondary outcomes were sleep quality (measured by Pittsburgh Sleep Quality Index, PSQI), anesthetic consumption, and treatment-related AEs.  After treatment, patients in the treatment group showed better outcomes in NRS (p < 0.01), PSQI (p < 0.01), and anesthetic consumption (p < 0.01), than patients in the control group.  No treatment-related AEs were documented in both groups in this study.  The authors concluded that this study found that UGPRF may be effective for alleviating pain intensity of ICN after LCS.

The authors stated that this retrospective study may suffer from several following drawbacks.  First, the sample size of this study was pretty small, which may impact the effect of UGPRF on ICN after LCS.  Second, this study only collected and analyzed outcome data before and after treatment.  No long-term follow-up outcome data following treatment was harvested and appraised.  Third, this retrospective study did not apply randomization and blind approaches to both patients and researchers, which may affect bias of patient selection.  Finally, the restriction of this study was its retrospective nature.  These researchers stated that future studies should avoid all these limitations.

Perineal Pain

Li and colleagues (2021) examined the safety and clinical efficacy of US-guided ganglion impar block (GIB)-PRF in the treatment of perineal pain.  A total of 30 patients with perineal pain were included and were treated by GIB-PRF guided by US imaging between January 2015 and December 2016.  Complications were recorded to observe the safety of the US-guided GIB-PRF procedure, and VAS scores at 24 hours before and after treatment and 1, 3, and 6 months later were analyzed to evaluate clinical efficacy.  Ultrasound-guided GIB-PRF was successfully carried out in all patients, and no complications occurred.  Compared with pre-treatment scores, the VAS scores were significantly lower (p < 0.05) at the 4 time-points after treatment.  The VAS scores at 1 and 3 months were slightly lower than those at 24 hours (p > 0.05) and were significantly lower at 6 months after treatment (p < 0.05).  There was a tendency toward lower VAS scores at 6 months after treatment compared with those at 1 and 3 months (p > 0.05).  The authors concluded that US-guided GIB-PRF was a safe and effective way to treat perineal pain.  The 6-month short-term clinical efficacy was favorable, but the long-term outcomes need future study.

The authors stated that this study had several drawbacks.  First, a relatively small sample size (n = 30) might have led to negative results, especially regarding post-treatment complications.  Furthermore, this study could not render a conclusion regarding the superiority of block alone or PRF alone versus combination of these 2 treatments, or US guidance versus X-ray guidance, which need further study.  Lastly, a follow-up of more than 6 months after the GIB-PRF is needed.

Periscapular Pain

Ergonenc and Beyaz (2018) examined the effects of pulsed radiofrequency (PRF) therapy of the supra-scapular nerve (SSN) under ultrasound (US) guidance in patients with chronic shoulder pain on both shoulder pain and function.  This study included 74 patients diagnosed with at least 1 of the following: adhesive capsulitis, rotator cuff syndrome and impingement syndrome of shoulder.  The PRF therapy of the SSN under US guidance was carried out in patients with a reduction of 50 % or more visual analog scale (VAS) score and those that reported healing in the active range of motion (AROM) in the diagnostic SSN block.  The resting, motion and sleeping shoulder pain assessments of the patients were performed with VAS score.  The shoulder joint function was evaluated with the Shoulder Pain and Disability Index (SPADI) questionnaire and the AROM of the joint was measured using a goniometer.  In 70 of the 74 patients a 50 % or more reduction was found in the VAS score with diagnostic SSN block.  After the PRF therapy of the SSN, the 15th day, 1st month, 3rd month, and 6th month follow-up VAS averages, SPADI averages and the flexion, internal rotation, external rotation, and abduction values were statistically significantly lower than the baseline values (p < 0.05).  The authors concluded that this study was the largest series in the literature examining the efficacy of PRF therapy of the SSN under US guidance and has shown that pain could be controlled quickly, for a long period of time, using US-guided PRF therapy of the SSN in chronic shoulder pain.

Esparza-Minana and Mazzinari (2019) stated that it has been estimated that 20 % of the general population will suffer shoulder pain throughout their lives, with a prevalence that can reach up to 50 %.  The SSN provides sensation for the posterior and superior regions of the glenohumeral joint, whereas the anterior and inferior zones and the skin are innervated mostly by the axillary nerve.  PRF on the SSN has been proposed as a therapeutic option in chronic shoulder pain.  Axillary nerve block has been proposed in the context of surgical analgesia as an adjuvant to SSN block.  They described the adaptation of a US-guided technique that targets both the suprascapular and axillary nerves for the treatment of painful shoulder syndrome.  The simultaneous PRF on the suprascapular and axillary nerves for the treatment of the chronic condition of shoulder pain has been scarcely studied, with very few references in the literature.  US-guided techniques target the nerve selectively, minimizing patients' and physicians' exposure to harmful radiation while increasing success rates by better needle placement.  These researchers performed both US-guided techniques with the patient in a lateral decubitus position with the affected shoulder on the upper side.  The authors concluded that by adapting an approach developed in acute pain management, they could safely deliver PRF to the suprascapular and axillary nerves for the treatment of shoulder pain.  This was a single-case study; and no follow-up data were provided.

In a prospective study, Lee et al (2020) examined the effectiveness of PRF with US guidance in patients with chronic cervical radicular pain that was refractory to repeated transforaminal epidural steroid injections (TFESIs).  This trial included 49 patients with chronic cervical radicular pain, unresponsive to repeated TFESIs, and who underwent PRF stimulation under US guidance.  Using US, a cannula was inserted toward the cervical spinal nerve.  The pain intensity was evaluated using the Numeric Rating Scale (NRS-11) for cervical radicular pain at pre-treatment and 1, 3, and 6 months post-treatment; and the Neck Disability Index (NDI) was used for evaluating functional disability before treatment and 6 months post-treatment.  Successful pain relief was defined as greater than or equal to 50 % reduction in the NRS-11 score as compared with the score before treatment.  Cervical radicular pain was significantly reduced at 1, 3, and 6 months post-PRF (p < 0.001).  At 6 months post-PRF, functional disability (NDI score) had significantly reduced, and 63.3 % of the patients achieved successful pain relief.  The authors concluded that PRF stimulation under the guidance of US is a potentially effective treatment method for managing refractory chronic cervical radicular pain.  These researchers stated that the main drawbacks of this study were the lack of a sham stimulation or control group, the small number (n = 49) of included patients and the lack of long-term follow-up.  They stated that further studies are needed to address these drawbacks.

Chung et al (2020) noted that suprascapular neuropathy is a rare cause of shoulder pain, and patients usually presents with postero-superior shoulder pain and weakness on forward flexion and external rotation.  Suprascapular neuropathy associated with rotator cuff pathology has received attention as an emerging cause of this condition.  SSN block can be used in these patients, and PRF can be applied to achieve a long-term effect.  Several studies have reported on PRF treatment of the SSN for shoulder pain, but most applied treatment to the nerve trunk under the transverse scapular ligament.  These investigators described a patient with suprascapular neuropathy treated with selective application of PRF to the distal SSN under US guidance.  The subject was a 68-year-old woman who suffered from right posterior shoulder pain after traumatic full thickness rotator cuff tear.  Her pain did not diminished despite of 2 surgeries.  She was diagnosed with entrapment of the distal SSN in the spino-glenoid notch (SGN) and suprascapular neuropathy.  The subject underwent surgery to decompress the entrapped SSN in the SGN.  After that, we applied PRF on the distal SSN under US guidance for persistent pain.  This treatment was repeated 3 times.  PRF treatment resulted in a slight reduction in the VAS pain score from 7to 8/10 to 5 to 6/10 at the 2 weeks follow-up, and to 2 to 3/10 at the 1-month follow-up.  The reduction in pain was maintained at the 1-year follow-up.  The authors concluded that PRF treatment of the SSN is typically approached from the main branch in the suprascapular notch.  These researchers selectively applied PRF to the distal SSN close to the SGN. This technique was safe and effective.  This was a single-case study with 1-year follow-up.  Moreover, these researchers stated that while applications of PRF to treat peripheral nerves have been increasing, clinical evidence of the efficacy of PRF for treating pain originating from peripheral nerves remains limited.

Cristiani and Hernandez (2020) reported on the case of a successful use of PRF in the treatment of refractory chronic shoulder pain in an adolescent patient.  These researchers presented a 53-kg, 14-year old girl, with a medical history of septic arthritis of the left shoulder within the 1st month of life leading to persisting pain during childhood.  She presented with a complaint of progressive pain starting at age 12, refractory to analgesics including opioids and intra-articular injection of local anesthetic and steroids.  After PRF of the SSN, significant pain relief and improvement of the ROM was obtained.  These results were maintained at the 1-, 3-, and 6-month follow-up visits with the pain being reported as mild and manageable with non-steroidal anti-inflammatory drugs (NSAIDs).  The authors concluded that there is limited data today of the use of PRF for pediatric chronic pain.  They successfully used this intervention in a 14-year old patient with chronic shoulder pain extrapolating from adult experience and as a last resort after all other treatments had failed.  These researchers stated that the positive results of this case report suggested that PRF may be effective in children and could be considered if the potential benefits outweigh the risks when non-invasive treatments fail.

Dey (2021) stated that chronic shoulder pain not relieved by either conservative or surgical management is referred to as chronic refractory shoulder pain.  In a retrospective case-series study, patients with chronic refractory shoulder pain were treated either with peripheral nerve stimulation (PNS) or with PRF therapy to the suprascapular nerve.  Both patients receiving PNS reported 100 % pain relief for the 1st month.  At the 3- and 6-month follow-ups, 1 patient continued to experience 100 % relief while the other reported 90 % relief; 1 patient undergoing PRF experienced about 90 % pain relief at both 1- and 3-month intervals and 0 % relief at the 6-month interval.  The other patient with PRF experienced 33 % relief at 1-month and 0 % relief thereafter.  No patient reported any complications.  The results of previous randomized controlled trials (RCTs) examining the effectiveness of PRF administered to the suprascapular nerve were mixed, and there is a lack of published studies on PNS effects.  The authors concluded that neuromodulation of the suprascapular nerve could be effective for chronic refractory shoulder pain patients; however, larger scale RCTs comparing PNS and PRF are needed to better understand their respective therapeutic capacity.

These researchers noted that a comparison between the 2 neuromodulation therapy techniques showed the 2 patients undergoing PNS therapy had better outcomes than the 2 patients with PRF therapy, in terms of both numeric pain rating and functional improvement-- especially at the 6-month interval.  However, this study’s sample size was too small to establish any clinically significant superiority for either therapy.  This study was a retrospective case report and hence the evidence obtained was less robust compared to that obtained with a prospective trial.  Furthermore, the small sample size (n = 2 for each group) and lack of racial or sex diversity in the sample made generalization of the study results to the general population difficult.  The follow-up period was limited to 6 months; thus, assumptions regarding the longer-term effectiveness of the neuromodulation techniques could not be made.

Pushparaj et al (2020) noted that studies have reported relief of chronic shoulder pain with non-ablative pulsed neuromodulatory (pRF) or ablative RF (aRF) procedures on innervation of the shoulder joint; however, interpretation of these reports is hampered by inconsistent indications, anatomic targets and follow-up.  In a systematic review, these researchers examined the available evidence on procedures employing pRF or aRF for treating chronic shoulder pain.  Medline and other medical literature databases were reviewed up to December 31, 2019 for publications on pRF or aRF procedures on shoulder joint innervation to relieve chronic pain.  Data on analgesic and functional outcomes measured at any time-point following the interventions were extracted.  Existing knowledge on innervation of the shoulder joint with relevance to RF procedures was also synthesized.  In all, 42 publications, 7 RCTs and 35 observational studies, case series or reports were identified; 36 of these publications were on pRF procedure and 29 of these reported procedures exclusively targeting the SSN.  A meta-analysis of the 7 RCTs evaluating pRF indicated no analgesic benefit or functional improvement with this treatment over conventional medical management.  Case series and reports on aRF indicated a potential for analgesic benefit but the quality of this evidence was low.  The authors concluded that RF treatments targeting the sensory innervation of the shoulder joint affected by degenerative conditions have the potential to reduce pain; however, the current evidence does not suggest analgesic or functional benefit (GRADE certainty of evidence-low); studies of high methodological quality are needed to further examine the role of these interventions.

Zoster-Related Pain

Wan and Song (2021) noted that PHN is the final stage of varicella zoster (VZ) infection and a severe refractory neuropathic pain.  Hence preventing transition of herpes zoster-related pain to PHN is a very important therapeutic principle for patients at an early stage, especially for older patients.  In a prospective, randomized, double-blinded study, these investigators examined the therapeutic efficacy and safety of PRF and stSCS in patients with acute/subacute VZ-related pain.  A total of 96 patients with acute/subacute VZ-related pain were equally randomized into 2 groups: PRF group and stSCS group.  Patients in the different groups were treated with high-voltage, long-duration PRF or stSCS.  The therapeutic effects were evaluated using NRS-11 and the 36-Item Short Form Health Survey (SF-36) at different time-points.  The average dose of pregabalin (mg/day) administrated at different time-points was also recorded.  The post-treatment NRS-11 scores in the 2 groups were significantly lower compared with baseline (p < 0.001).  The NRS-11 scores in the stSCS group were significantly lower than those in the PRF group at 30 and 180 days after treatments (p < 0.05).  The SF-36 scores of general health, social function, role-emotional, mental health, bodily pain, physical function, physical role, and vitality could be significantly improved at each time-point after treatments in the 2 groups.  Some SF-36 scores could be significantly improved at some time-points in the stSCS group compared with the PRF group.  The rescue drug (pregabalin) dosages were lower in the stSCS group than those in the PRF group at days 90 and 180 after treatments.  There was no bleeding at the puncture site, infection, post-operative paresthesia, nerve injury, or any other serious adverse effects in either group.  The authors concluded that PRF and stSCS were both safe and effective therapeutic alternatives for patients with acute/subacute VZ-related pain, however, stSCS could achieve more pain relief and improvement of QOL compared with PRF. 

The authors stated that this study had several drawbacks.  First, patients enrolled were from only 1 pain management center and the number of patients was relatively small.  Second, subjects were followed-up only for 180 days.  These researchers stated that future study should be a research across multiple centers with a longer follow-up. 

Xue et al (2022) stated that recent studies have shown that short-term spinal cord stimulation (stSCS) can effectively alleviate zoster-related pain.  Due to the lack of evidence, it is unclear if stSCS is superior to PRF in treating zoster-related pain.  In a systematic review and meta-analysis, these researchers compared the safety and effectiveness of stSCS and PRF for zoster-related pain.  They searched 7 electronic databases from the establishment of the database to January 2021.  Related RCTs were included in this meta-analysis.  After extracting the data and examining the methodological quality of the included trials, the outcome indicators were statistically analyzed by using RevManV.5.3.  This meta-analysis included 6 trials with a total of 509 patients.  Compared with PRF group, stSCS group showed lower pain intensity (standardized mean difference [SMD] = -0.83, 95 % CI: -1.37 to -0.30, p = 0.002), better sleep quality (MD = -1.43, 95 % CI: -2.29 to -0.57, p = 0.001), lower pain rating index scores, and less incidence of AEs (RR = 0.32, 95 % CI: 0.12 to 0.83, p < 0.05).  However, the efficacies of PRF and stSCS for treating PHN were consistent in the response rate (RR = 1.10, 95 % CI: 0.82 to 1.48], p = 0.51) and the complete remission (CR) rate (RR = 1.05, 95 % CI: 0.66 to 1.68], p = 0.84).  The authors concluded that stSCS showed a better analgesic effect and higher safety than PRF.  They stated that the findings of this meta-analysis suggested that stSCS may be a feasible and safe invasive treatment for zoster-related pain.  Moreover, these researchers stated that high-quality RCTs with large sample sizes are needed to validate these findings.

Chronic Hip Pain

Jadon (2021) stated that pericapsular nerve group (PENG) block is a novel US-guided block that is primarily used for acute pain management in the hip fractures.  These investigators reported a case where the PENG block was used for the chronic hip pain with adductor spasm due to hip OA.  The PENG block with a combination of local anesthetic and steroids provided an effective pain relief; however, only for shorter duration.  After 2 attempts of the PENG block with local anesthetic and steroids mixture, PRF of the PENG was carried out, which provided the long-lasting relief.  The authors concluded that the findings of this study suggested that US-guided PRF of the PENG provided effective and prolonged pain relief in chronic hip pain of OA.  These preliminary findings from a single-case study need to be validated by well-designed studies.

Lumbar Herniated Nucleus Pulposus

Marliana et al (2021) noted that RF therapy is a medical procedure mainly used to reduce pain with a low complication rate (less than 1 %), ease of application, and low cost.  In a systematic review and meta-analysis, these researchers examined the effectiveness of PRF in treating radicular pain and evaluated the safety of PRF in managing radicular pain in lumbar herniated nucleus pulposus (HNP).  A total of 6 full articles with the following features were selected for this review: Articles published in English; studies on the PRF effect on radicular pain in lumbar HNP; and RCTs.  The studies showed that the PRF group had a reduction in pain scores at each evaluation.  In 4 studies, the PRF group showed a more significant reduction in pain scores than the control, and in 2 of the studies, the reduction in pain scores was not significant in the PRF group compared to the control.  An adverse effect was reported in 1 patient experiencing increased radicular pain following PRF.  There was a lack of data needed for statistical analysis, and the lack of a uniform duration for the PRF procedure by all the studies.  The authors concluded that PRF could be used as a promising clinical recommendation for pain management with minimally invasive radicular pain techniques due to lumbar HNP.

Post-Herpetic Neuralgia

In a prospective, double-blind, single-center RCT, Li et al (2022) compared the effectiveness of PRF alone versus a combination of PRF and dexamethasone (DEX) for the treatment of trigeminal PHN.  A total of 103 patients diagnosed with trigeminal PHN were randomly assigned into 2 groups (the PRF group and PRF plus DEX [PRF+D] group).  Digital subtraction angiography-guided puncture of the Gasserian ganglion was carried out.  All patients received PRF of the Gasserian ganglion first, and then a local injection was administered into the Gasserian ganglion.  Patients in the PRF+D group received PRF therapy and 1-ml of 5-mg DEX in the Gasserian ganglion, while patients in the PRF group received PRF therapy and 1-ml of normal saline in the Gasserian ganglion.  The primary outcome was pain intensity, measured by the VAS.  The secondary outcome was QOL, assessed by the SF-36.  The dosage of pregabalin administered was recorded to examine the effectiveness of treatment.  Compared with the PRF group, the PRF+D group showed more promising outcome results in pain relief as measured by the VAS; QOL enhancement, as measured by the SF-36; and a reduced requirement for anti-epileptic drugs (p < 0.01).  The authors concluded that the effectiveness of PRF combined with a DEX injection into the Gasserian ganglion was superior to that of PRF {and saline injection} alone of the Gasserian ganglion for trigeminal PHN.  These investigators stated that the 2 main drawbacks of this trial were that it was a single-center study, and the relatively small number of patients.

Tinnitus

Koning and van Hemert (2022) stated that vagal nerve stimulation (VNS) is a promising therapy for tinnitus; PRF is a minimally invasive neuromodulator technique that could be applied repeatedly without damage to neural tissue.  In a single-case study, these investigators documented the use of PRF of the vagal nerve as a successful therapy without harm for patients with tinnitus.  A 22-G needle (60 mm-long with a 5-mm active tip) was placed percutaneously at the inner side of the tragus.  The auricular branch of the vagal nerve was subjected to PRF at 42-V, 2-Hz, and 10-milliseconds for 10 mins.  PRF of the vagal nerve can reduced tinnitus and improved hearing in a patient with severe tinnitus and hearing loss.  The intensity of the tinnitus was reduced to 5 % of the original intensity at the left side and to 20 % at the right side.  An improved hearing of 20 to 30 dB from 250 Hz to 8 kHz in the left ear and from 250 Hz to 2 kHz in the right ear was objectivated in the audiogram.  The authors concluded that PRF of the vagal nerve could reduce tinnitus and improve hearing in a patient with severe tinnitus and hearing loss.  Moreover, these researchers stated that further research of PRF of the vagal nerve in tinnitus patients is needed.

Trigeminal Neuralgia

Zhang et al (2022) noted that conventional RF (CRF), PRF, and pulsed combined conventional RF (PCRF) are widely used in the clinical treatment of TN; however, collective evidence comparing the safety and effectiveness of these RF therapies is still controversial.  In a systematic review and meta-analysis, these investigators provided additional evidence for the safety and effectiveness of different RF therapies in the management of TN.  Systematic database research on double-blind RCTs was carried out based on PubMed, Embase, and Web of Science.  Literature on TN in adults under different RF therapies was collected to evaluate pain scores, excellent pain relief, and occurrence of adverse effects after corresponding therapies.  A total of 11 studies, including 570 patients, were involved in this systematic review; 2 studies from the same research team and 1 study with a completely different pain assessment tool were excluded from the meta-analysis.  A total of 8 studies, including 412 samples, were included in the quantitative synthesis.  In secondary analyses, these researchers also observed a safer outcome in PRF than CRF when regarding the occurrence of adverse effects.  Nevertheless, despite no statistical difference in pain scores between CRF and PRF 1 week after surgery, a positive impact was observed in the CRF group 1 month and 3 months after surgery.  A meta-analysis of 6 studies comparing PCRF and CRF was performed and revealed no evidence to prove excellent pain relief of PCRF and CRF groups at 6 months, 1 year, and 2 years after surgery.  However, a positive influence in reducing pain scores was observed in the PCRF group.  Subgroup analysis further exhibited that PCRF positively affected TN when the temperature was lower than 70°C.  The authors concluded that PCRF provided better long-term effectiveness and fewer adverse effects for treating TN.  Yet, it is hard to draw definitive conclusions regarding excellent pain relief comparisons due to the moderate quality of evidence, high heterogeneity, as well as scarcity of available data.

The authors stated that this review/meta-analysis had several drawbacks.  First, a small overall sample of included trials.  Second, the diversity of tools used for pain assessment across studies, such as Barrow Neurological Institute (BNI) pain intensity scale, NRS, and VAS limited the evaluation of outcomes. Third,  a high risk exists for most studies in the meta-analysis for at least 1 domain, which may have affected the reliability of results.  Fourth, the short follow-up period of a few studies in the meta-analysis while the long-term effectiveness of different RF treatments may require longer follow-up data to enhance the accuracy of the assessment.

References

The above policy is based on the following references:

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