Quantitative Sensory Testing Methods

Number: 0357

(Replaces CPB 385)

 

Table Of Contents

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

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses quantitative sensory testing methods.

Experimental, Investigational, or Unproven

The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:

1. Quantitative sensory testing (QST), also known as pressure-specified sensory device testing, for the following because its diagnostic value has not been established (not an all-inclusive list):
   
   
   1. Detection of hyperalgesia in chronic pain individuals on long-term opioids
   2. Diagnosis of restless legs syndrome/Willis-Ekbom disease
   3. Diagnosis of small fiber neuropathy in postural orthostatic tachycardia syndrome
   4. Evaluation of acute musculoskeletal pain post-surgery or post-injury
   5. Evaluation of carpal tunnel syndrome/musculoskeletal pain/trigeminal neuralgia
   6. Evaluation of chronic itch
   7. Evaluation of chronic pelvic pain
   8. Evaluation of fibromyalgia pain
   9. Evaluation of lumbar radiculopathy
   10. Evaluation of pain intensity or disability in chronic pain
   11. Evaluation of POEMS syndrome
   12. Evaluation of shoulder pain
   13. Evaluation of temporal changes in pain processing following whiplash injury to identify the risk for chronification
   14. Evaluation of tumor-related cancer pain
   15. Evaluation of women after surgery for breast cancer
   16. Management of individuals with neuropathy
   17. Prediction of outcome in low back pain
   18. Prediction of post-operative pain
   19. Prediction of the response to opioid treatment.

2. Current perception threshold (CPT) testing because the clinical applicability of this testing in diagnosing and/or managing diabetic peripheral neuropathy, restless legs syndrome/Willis-Ekbom disease, or other diseases has not been established.

3. Voltage-actuated sensory nerve conduction threshold (VsNCT) testing (e.g., by means of the Medi-Dx 7000 or the Neural-Scan) because its clinical value has not been established in the peer-reviewed published medical literature.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes not covered for indications listed in the CPB:
0106T	Quantitative sensory testing (QST), testing and interpretation per extremity; using touch pressure stimuli to assess large diameter sensation
0107T	using vibration stimuli to assess large diameter fiber sensation
0108T	using cooling stimuli to assess small nerve fiber sensation and hyperalgesia
0109T	using heat-pain stimuli to assess small nerve fiber sensation and hyperalgesia
0110T	using other stimuli to assess sensation
Other CPT codes related to the CPB:
95907 - 95913	Nerve conduction studies
95925 - 95927	Short-latency somatosensory evoked potential study, stimulation of any/all peripheral nerves or skin sites, recording from the central nervous system
HCPCS codes not covered for indications listed in the CPB:
G0255	Current perception threshold/sensory nerve conduction test, (SNCT), per limb, any nerve
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
C50.011- C50.919	Malignant neoplasm of breast
D47.Z9	Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue [POEMS]
E10.40 - E10.49 E11.40 - E11.49	Diabetes with neurological complications
G25.81	Restless legs syndrome [Willis-Ekbom disease]
G50.0 - G59	Nerve, nerve root and plexus disorders
G62.89	Other specified polyneuropathies [small fiber neuropathy]
G62.9	Polyneuropathy, unspecified [POEMS]
G89.11-G89.18	Acute pain [Post-operative pain]
G89.21 - G89.29	Chronic pain
G89.3	Neoplasm related pain (acute) (chronic)
I49.8	Other specified cardiac arrhythmias [postural orthostatic tachycardia]
L29.0 - L29.9	Pruritus [chronic itch]
M25.511 – M25.519	Pain in shoulder
M50.00 - M54.9	Other dorsopathies
M60.001 - M60.19	Myositis
M79.7	Fibromyalgia
M79.10 - M79.2	Myalgia, neuralgia and neuritis, unspecified
R10.2	Pelvic and perineal pain [chronic]
R20.0 - R20.9	Disturbances of skin sensation
S13.4XXA- S13.4XXS	Sprain of ligaments of cervical spine [Whiplash injury]
Z79.899	Other long term (current) drug therapy

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Background

1. touch-pressure,
2. vibration, and
3. coolness, warmth, cold pain, and heat pain.

In QST, the subject must be able to comprehend what is being asked by the test, alert and not taking mind-altering medications, and not biased to a certain test outcome.

Abnormal or elevated QST measurements are not specific in the diagnosis of any particular type of neuropathy, and in fact do not necessarily indicate any form of peripheral neuropathy.  There are no prospective clinical studies demonstrating that quantitative tests of sensation improve the management and clinical outcomes of patients over standard qualitative methods of sensory testing.

The vibrometer is a device used for measuring sensation/sensitivity to vibration.  Testing of vibration sense can be adequately performed with a tuning fork of 128 Hz.

The American Academy of Neurology evaluated the clinical utility, efficacy, and safety of QST (Shy et al, 2003).  The authors concluded that QST is a potentially useful tool for measuring sensory impairment for clinical and research studies.  However, QST results should not be the sole criteria used to diagnose pathology.  Because malingering and other non-organic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters.  The authors stated that well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

The American Association of Electrodiagnostic Medicine (Chong and Cros, 2004) stated that available literature data do not allow conclusions regarding the relative merits of individual QST instruments.

Eisenberg and colleagues (2010) used both static and dynamic QST on 40 healthy volunteers in order to examine if this methodology can predict the analgesic effects of oral oxycodone, as compared to a placebo, on latency to onset, pain intensity, and tolerance to the cold pressor test.  Static QST consisted of measuring heat and cold pain thresholds.  Dynamic QST included measurements of the magnitude of the diffuse noxious inhibitory control (DNIC)-like effect and of temporal summation (TS).  Results showed that oxycodone, but not the placebo, significantly elevated the latency and tolerance to cold pain and significantly reduced pain intensity.  The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment (F((1,22)) = 5.63, p = 0.027, R(2) = 0.17).  The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to cold pressor test (F((1,38)) = 9.11, p = 0.005, R(2) = 0.17).  These results suggested that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment.  The findings of this study need to be validated especially in patients with addiction.

Pavlakovic and Petzke (2010) noted that QST is a non-invasive method of assessing sensory and pain perception that has been used in the past 30 years primarily for analysis of cutaneous and mucosal perception.  In recent years, several published studies have demonstrated that QST may be useful in the analysis of painful musculo-skeletal disorders as well.  Based on the results of these studies, it can be postulated that QST may be useful in the analysis of the pathogenesis, classification, and differential diagnosis of musculo-skeletal disorders.  However, due to the diverse etiopathogenetic basis of these disorders, a broad range of QST test batteries may be necessary to analyze the various musculo-skeletal disease entities.  These researchers analyzed published studies on this subject and summarized current information on altered sensory and pain perception available for some of the most common musculo-skeletal disorders.  The authors concluded that at present, QST remains primarily a research tool but may be useful in differential diagnosis in indicating the presence of central sensitization and for clinical monitoring of disease progression or treatment response.

In a review on the usefulness and limitations of QST in neuropathic pain states, Hansson et al (2007) stated that there is a lack of specificity of current QST databases; thus QST can not be used alone for diagnosis of a neurological lesion.  The authors also noted that QST is not useful in predicting which patients with post-herpetic neuralgia (PHN) or peripheral neuropathy would benefit from lidocaine patches.  Also, serial QST evaluations in patients with acute herpes zoster failed to predict who would develop PHN.  Furthermore, the authors stated that the expected role of QST in the definition of a mechanisms-based approach to neuropathic pain has not yet been met.

Hubscher et al (2013) stated that sensitization of the nervous system can present as pain hypersensitivity that may contribute to clinical pain.  In spinal pain, however, the relationship between sensory hypersensitivity and clinical pain remains unclear.  This systematic review examined the relationship between pain sensitivity measured via QST and self-reported pain or pain-related disability in people with spinal pain.  Electronic databases and reference lists were searched.  Correlation coefficients for the relationship between QST and pain intensity or disability were pooled using random effects models.  Subgroup analyses and mixed effects meta-regression were used to examine if the strength of the relationship was moderated by variables related to the QST method or pain condition.  A total of 145 effect sizes from 40 studies were included in the meta-analysis.  Pooled estimates for the correlation between pain threshold and pain intensity were -0.15 (95 % confidence interval [CI]: -0.18 to -0.11) and for disability -0.16 (95 % CI: -0.22 to -0.10).  Subgroup analyses and meta-regression did not provide evidence that these relationships were moderated by the QST testing site (primary pain/remote), pain condition (back/neck pain), pain type (acute/chronic), or type of pain induction stimulus (e.g., mechanical/thermal).  Fair correlations were found for the relationship between pain intensity and thermal temporal summation (0.26, 95 % CI: 0.09 to 0.42) or pain tolerance (-0.30, 95 % CI: -0.45 to -0.13), but only a few studies were available.  The authors concluded that the findings of this study indicated either that pain threshold is a poor marker of central sensitization or that sensitization does not play a major role in patients' reporting of pain and disability.  

1. heat pain threshold in experimental human pain,
2. electrical and heat pain thresholds, pressure pain tolerance and supra-threshold heat pain in surgical patients, and
3. electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain.

Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics.  The authors concluded that although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response.  Moreover, they stated that future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm.

Werner et al (2013) stated that QST investigates the graded psychophysical response to controlled thermal, mechanical, electrical or chemical stimuli, allowing quantification of clinically relevant perception and pain thresholds.  The methods are ubiquitously used in experimental and clinical pain research, and therefore, the need for uniform assessment procedures has been emphasized.  However, varying consistency and transparency in the statistical methodology seem to occur in the QST literature.  A total of 16 publications, evaluating aspects of QST variability, from 2010 to 2012, were critically reviewed in detail.  A considerable heterogeneity in the statistical evaluations of test-retest data was demonstrated.  The authors, using a secondary analysis of published data for didactic purposes, proposed and presented minimal requirements for reporting of test-retest QST data.

Cruz-Almeida and Fillingim (2014) summarized the scientific literature relating to the use of QST for mechanism-based pain management.  A literature search was undertaken using PubMed and search terms including quantitative sensory testing, pain, chronic pain, response to treatment, outcome measure.  Studies including QST in healthy individuals and those with painful disorders were reviewed.  Publications reported on QST methodological issues including associations among measures and reliability.  These investigators also included publications on the use of QST measures in case-control studies, their associations with bio-psychosocial mechanisms, QST measures predicting clinical pain, as well as predicting and reflecting treatment responses.  Although evidence suggests that QST may be useful in a mechanism-based classification of pain, there are gaps in the current understanding that need to be addressed including making QST more applicable in clinical settings.  There is a need for developing shorter QST protocols that are clinically predictive of various pain subtypes and treatment responses without requiring expensive equipment.  The authors concluded that future studies are needed, examining the clinical predictive value of QST including sensitivity and specificity for pain classification or outcome prediction.  These findings could enable third-party payers' reimbursement, which would facilitate clinical implementation of QST.  Moreover, they stated that with some developments, QST could become a cost-effective and clinically useful component of pain assessment and diagnosis, which can further the progress toward the goal of mechanism-based personalized pain management.

The Washington State Department of Labor and Industries’ guideline on “Work-related carpal tunnel syndrome diagnosis and treatment guideline” (2014) stated that “The department does not cover quantitative sensory tests”.

Katz et al (2015) noted that opioid-induced hyperalgesia is a clinical syndrome whereby patients on long-term opioids become more sensitive to pain while taking opioids.  Opioid-induced hyperalgesia is characterized by increased pain intensity over time, spreading of pain to other locations, and increased pain sensation to external stimuli.  To characterize opioid-induced hyperalgesia, laboratory methods to measure hyperalgesia have been developed.  To determine the performance of these methods, these researchers conducted a systematic review of clinical studies that incorporate measures of hyperalgesia in chronic pain patients on long-term opioids.  PubMed and Cochrane databases were searched (terms: opioid induced hyperalgesia, study or trial, and long-term or chronic).  Studies published in English were selected if they were conducted in chronic pain patients on long-term opioids and incorporated measures of hyperalgesia; acute/single-dose studies and/or conducted in healthy volunteers were excluded.  A total of 14 articles made the final selection (11 were selected from the search and 3 others were found from additional sources); there was 1 randomized controlled trial (RCT), 1 prospective controlled study, 3 prospective uncontrolled studies, and 9 cross-sectional observation studies.  Hyperalgesia measurement paradigms used included cold pain, heat pain, pressure pain, electrical pain, ischemic pain, and injection pain.  Although none of the stimuli was capable of detecting patients' hyperalgesia, heat pain sensitivity showed some promising results.  The authors concluded that none of the measures reviewed met the criteria of a definitive standard for the measurement of hyperalgesia.  They stated that additional studies that use improved study design should be conducted.

Current perception threshold (CPT) testing (also known as sensory nerve conduction threshold testing) entails the quantification of the sensory threshold to transcutaneous electrical stimulation.  It has been used to examine sensory nerves.  In general, CPT testing falls into the general category of QST.  CPT testing has been studied for a wide range of clinical applications such as evaluation of peripheral neuropathies, detection of carpal tunnel syndrome, spinal radiculopathy, evaluation of the effectiveness of peripheral nerve blocks, quantification of hypoesthetic and hyperesthetic conditions and differentiation of psychogenic from neurological disorders.  The AXON-II NCSs System (PainDx, Inc., Laguna Beach, CA), Neurometer^® Current Perception Threshold (Neurotron, Inc., Baltimore, MD) and the Medi-Dx 7000^™ (Neuro Diagnostic Associates, Inc., Laguna Beach, CA) are devices cleared by the Food and Drug Administration (FDA) through the 510k process for the use of measuring the threshold for sensory nerve conduction. Thus, the manufacturers were not required to present evidence of efficacy to support a premarket approval application (PMA). These devices have been used to detect metabolic, toxic, acquired, hereditary, compression, traumatic, and other peripheral neuropathies as well as sensory impairments resulting from central nervous system pathology.  However, the effectiveness and clinical applicability of CPT testing in diagnosing and/or managing a disease has not been established.

A study by Tack et al (1994) compared CPT testing at different frequencies with standardized clinical examination scores.  The authors concluded that CPT testing “seemed rather insensitive at detecting neuropathy”.  Compared with standard clinical examination, CPT testing “is only of limited value, mainly because of high variability and poor reproducibility”.

Yilmaz et al (2010) compared sensory thresholds in different nerve-fiber types in men with chronic pelvic pain syndrome (CPPS) and healthy controls, using thermal sensory testing and measuring CPT.  These researchers enrolled 22 men with CPPS and 20 healthy control participants.  They determined the thermal sensory perception thresholds of C and Adelta nerve fibers on the perineum and left posterior thigh.  To test CPT, they used sine wave electrical stimulation at 5-Hz, 250-Hz, and 2,000-Hz, resulting in the selective depolarization of small unmyelinated C fibers, small myelinated Adelta, and large myelinated Abeta fibers, respectively.  These researchers bilaterally tested the hypothenar surface of the palms, medial parts of soles, mid-shaft of penis, and 1 site in the mid-perineum, for a total of 7 sites.  The mean age of men with CPPS was similar to that of controls [42.8 (standard deviation, 9.4) and 40.4 (standard deviation, 13.2) years, respectively, p = 0.548].  There was no significant difference between the 2 groups for thermal perception thresholds in both the perineum and left thigh (p > 0.05).  There was also no difference between the 2 groups for CPT values of all 3 frequencies of stimuli in each area tested (p > 0.05 for all comparisons).  The authors concluded that the absence of sensory threshold differences between men with CPPS and controls, with either thermal stimulation of C and Adelta fiber afferents or electrical stimulation of C, Adelta, and Abeta fiber afferents, discounts the existence of a peripheral neuropathy as a cause for pain in men with CPPS.

Liao et al (2010) recruited 49 patients with classical trigeminal neuralgia (TN) according to the latest guidelines of the International Classification of Headache Disorders, and divided them into an acute (less than or equal to 30 days onset; n = 13) and a chronic (greater than 30 days onset; n = 36) group.  These investigators used blink reflex study and CPT testing to evaluate the painful facial areas and contralateral non-painful areas of patients with classical TN.  Current perception threshold 5-Hz examinations, which correlate with unmyelinated fiber function, showed significantly decreased CPTs in the acute stage (11.62 +/- 6.99 versus 18.69 +/- 9.66, p = 0.025), but significantly increased CPTs in the chronic stage (26.67 +/- 18.65 versus 19.69 +/- 13.70, p = 0.010) on the painful side when compared with the contralateral non-painful side.  However, CPTs at 250-Hz (Adelta) and 2,000-Hz (Abeta) examinations did not show significant differences between the painful and non-painful sides.  In contrast, only 3 (3/49) patients showed an abnormal trigeminal nerve stimulation on the ipsilateral painful side by blink reflex study.

An assessment on the use of electroneurometer in the diagnosis of carpal tunnel syndrome (CTS) conducted by the American Association of Electrodiagnostic Medicine (David et al, 2003) reached the following conclusions: "It is the opinion of the American Association of Electrodiagnostic Medicine (AAEM) that all of the literature reviewed and describing the nervepace digital electroneurometer (NDE) and neurosentinel (NS) are flawed.  Limb temperature, which affects the speed of nerve conduction, was controlled in only one study.  In most reports, reference populations were not studied to provide a scientifically based source for control values.  Standard statistical measures of latency values (mean, standard deviation, and range) were not specified in most reports.  Moreover, most studies comparing NDE and NS to standard nerve conduction studies (NCSs) make an incorrect assumption: that distal motor latency or an isolated digital sensory latency values are sensitive measures for diagnosing median nerve entrapment at the wrist.  In fact, detailed sensory NCSs, including segmental stimulation across the palm-to-wrist segment or in comparison to adjacent sensory nerves, is by far the more sensitive technique in this regard and is probably the earliest finding in median nerve entrapment at the wrist.  It is the opinion of the AAEM that the NDE, as well as the newer NS, are experimental and are not effective substitutes for standard electrodiagnostic studies in clinical evaluation of patients with suspected CTS."

The Medi-Dx 7000 (Neuro Diagnostic Associates) is a voltage-actuated sensory nerve conduction test (VsNCT) device.  The device was cleared by the FDA based on a 510(k) application.  An updated version of the Medi-DX 7000 is the Neural-Scan (Neuro Diagnostic Associates, Inc.), which is a current potential threshold test with a potentiometer.  The V-sNCT measures the voltage amplitude necessary to cause a discernable nerve impulse.  VsNCT results are adjusted and compared to population means.  The most severe hypoesthesia is considered the primary lesion.  There is no peer-reviewed published medical literature on the use of voltage-actuated sensory nerve conduction tests and their impact on clinical outcomes.

In March 2004, the Center for Medicare and Medicaid Services (CMS) re-affirmed its non-coverage policy on the CPT and sensory nerve conduction threshold test (sNCT); CMS (2004) concluded that “there continues to be insufficient scientific or clinical evidence to consider the sNCT test and the device used in performing this test as reasonable and necessary”.

A study by Cork et al (2002) reports on the performance characteristics of vSNCT using the Medi-Dx 7000 and physical examination findings for predicting nerve root pathology on an epidurogram.  The study has a number of flaws, in particular lack of blinding, and does not report on improvements in clinical outcomes with use of vSNCT.  It should be noted that the study was published in a journal that not indexed by the National Library of Medicine in the PubMed database of peer-reviewed published medical literature.

In addition, it should be noted that CPT code 95904 is not the correct code to bill for V-SNCT. CPT code 0110T (“Quantitative sensory testing (QST), testing and interpretation per extremity; using other stimuli to assess sensation”) or G0255 (“Current perception threshold/sensory nerve conduction test, (SNCT) per limb, any nerve”) should be used to bill for this service.

Pressure-specified sensory testing is a technique employed to evaluate nerve function by quantifying the thresholds of pressure detected with light, static, and moving touch.  The Pressure-Specified Sensory Device (PSSD) (Sensory Management Services LLC, Baltimore, MD) was cleared for marketing by the FDA in 1994.  It consists of 1 or 2 probes and transducers for measuring and recording the perception thresholds of pressure on the surface of the body in g/mm2.  This method is a modification of the 2-point discrimination methodology.  The device has been used to assist in the diagnosis and assessment of nerve function, including diabetic peripheral neuropathy, carpal tunnel syndrome (CTS), and other nerve entrapment or compression syndromes, as well as post-operative assessment of sensory outcomes following liposuction, breast reduction mammoplasty, etc.

Siemionow et al (2006) stated that diabetic patients are more susceptible to the development of entrapment neuropathy than non-diabetics.  Since these patients suffer from a slowly progressing diabetic polyneuropathy, standard neurosensory and motor tests of nerve function are insufficient in the diagnosis of super-imposed nerve compression.  This is most evident in the early stages of compression when quantitative diagnosis is important for making decisions on surgical decompression.  These researchers evaluated the validity of computer-assisted PSSD testing in the early detection of super-imposed entrapment in diabetic neuropathy in comparison with standard clinical tests.  A total of 25 diabetic patients with complaints of peripheral nerve dysfunction were evaluated by clinical tests and PSSD.  Out of those, nerve entrapment was detected in 15 patients (60 %) (9 in late stage and 6 in early stage) by neurosensory PSSD testing.  Standard clinical tests were confirmative in 33.3 % of these cases (44 % of late and 16.7 % of early stage).  Out of 144 evaluated nerves, 50 were diagnosed with entrapment (24 in late and 26 in early stage) using PSSD.  Clinically, diagnosis was confirmed in 16 % of entrapped nerves (20.8 % of late and 11.5 % of early stage).  Average diabetes duration in patients with entrapment diagnosed using PSSD was significantly shorter than for those diagnosed clinically (4.14 +/- 2.04 versus 7.2 +/- 1.3 years, respectively; p = 0.005).  Among evaluated factors, mean age and diabetes duration were found to be significantly shorter in patients with entrapment than in those with advanced diffused changes (54.47 +/- 13.07 versus 67.10 +/- 14.2 years; p = 0.019 and 5.33 +/- 3.74 versus 14.22 +/- 8.17 years; p = 0.006; respectively).  The authors concluded that these results revealed higher sensitivity of PSSD in comparison with standard clinical tests in the detection of early-stage entrapment in patients with diabetes.  Moreover, they stated that to assess accuracy of PSSD in the proper patients' qualification for surgery, further prospective, post-operative studies are needed.

Slutsky (2009) reported the findings of 69 patients with signs of CTS who underwent nerve conduction studies (NCS) and testing with the PSSD.  A total of 102 tests were performed (28 bilateral).  Twenty patients underwent a carpal tunnel release and were retested after 4 to 6 months.  The Symptom Severity Score (SSS) was calculated before and after surgery.  A control group of 20 hands in 10 asymptomatic volunteers underwent identical testing.  The NCS sensitivity was 87 % with a specificity of 90 % whereas the PSSD sensitivity was 81 % with a specificity of 65 %.  The combined sensitivity of the 2 tests was 93 %.  In the operative group the SSS improved from a mean of 3.34 pre-operatively to 1.95 post-operatively.  The NCS improved in 19/21 hands whereas the PSSD improved in 16/19 hands.  The non-invasive SSS and PSSD can increase the diagnostic yield in CTS, especially when the NCS are normal.

Nath et al (2010) stated that brachial plexus upper trunk injury is associated with winged scapula owing to the close anatomical course of the long thoracic nerve and upper trunk.  Needle electromyography (EMG) is a common diagnostic test for this injury; however, it does not detect injury in most patients with upper trunk damage.  The PSSD may be an alternative to needle EMG.  In this study, a total of 30 patients with winged scapula and upper trunk injury were evaluated with needle EMG and PSSD.  Needle EMG testing of the biceps muscle was compared with PSSD testing of the dorsal hand skin (C6 damage), and EMG testing of the deltoid and spinati muscles was compared with PSSD testing of the deltoid skin (C5 damage).  Pressure values measured by PSSD were significantly higher on the affected arm.  The authors concluded that PSSD tests consistently identified injuries that were not detected by needle EMG tests.  They stated that these findings provided evidence that the PSSD is more effective than needle EMG in the detection of brachial plexus upper trunk injury.  The findings of this small uncontrolled study need to be confirmed by further investigation.

Sever et al (2013) noted that intra-neural fibrolipoma is a benign, uncommon tumor that is characterized with infiltration of the epineurium and perineurium by fibro-fatty tissue; pre-operative diagnosis is difficult.  However, the Pressure-Specified Sensory Device (PSSD) may support identifying the earliest stages of intra-neural fibrolipoma when traditional electro-diagnostic testing is unable to detect a change in peripheral nerve function.  These researchers reported the use of PSSD in the evaluation of motor and sensorial functions in patients with intra-neural fibrolipoma.  Five patients (3 males, aged 23 to 53; mean of 41 years) with intra-neural fibrolipoma were operated on.  Grip strength, pinch strength and sensorial functions were assessed in all patients before surgery and at the end of the follow-up period by PSSD.  Patients were followed-up for 7 to 24 months (mean of 12 month).  All of the patients improved dramatically following the operation and they had total relief of pain and paresthesia.  The authors concluded that decompression of intra-neural fibrolipoma of the nerve with limited excision and epineurotomy without sacrificing the main nerve and its branches is the ideal surgical procedure.  They recommended the use of PSSD in the investigation of patients with peripheral nerve compression, and chronic unusual volar forearm and wrist swelling.  They stated that PSSD is an important tool for pre-operative evaluation and diagnosis of intra-neural fibrolipoma.  The findings of this case-series study need to be validated by well-designed studies.

Quantitative Sensory Testing for Low Back Pain

Marcuzzi and colleagues (2016) stated that QST measures have recently been shown to predict outcomes in various musculoskeletal and pain conditions.  These researchers summarized the emerging body of evidence examining the prognostic value of QST measures in people with low back pain (LBP).  The protocol for this review was prospectively registered on the International Prospective Register of Systematic Reviews.  An electronic search of 6 databases was conducted from inception to October 2015.  Experts in the field were contacted to retrieve additional unpublished data.  Studies were included if they were prospective longitudinal in design, assessed at least one QST measure in people with LBP, assessed LBP status at follow-up, and reported the association of QST data with LBP status at follow-up.  Statistical pooling of results was not possible due to heterogeneity between studies.  Of 6,408 references screened after duplicates removed, 3 studies were finally included.  None of them reported a significant association between the QST measures assessed and the LBP outcome.  Three areas at high risk of bias were identified which potentially compromised the validity of these results.  The authors concluded that due to the paucity of available studies and the methodological shortcomings identified, it remains unknown whether QST measures are predictive of outcome in LBP.

Quantitative Sensory Testing for Trigeminal Neuralgia

In an observational study, Flor and associates (2016) used QST to detect abnormalities in sensory processing in patients with trigeminal neuralgia (TN) by comparing the affected and non-affected nerve branches with their contralateral counterparts and by comparing the results of the patients with those of controls.  Quantitative sensory testing was conducted on 48 patients with idiopathic TN and 27 controls matched for age and gender using the standardized protocol of the German Neuropathic Pain Network.  Stimulations were performed bilaterally in the distribution of the trigeminal branches.  Patients had no prior invasive treatment, and medications at the time of examination were noted.  In patients with TN, deficits in warm and cold sensory detection thresholds in the affected and also the non-affected nerve branches were found.  Tactile sensation thresholds were elevated in the involved nerve branches compared to the contralateral side.  The authors concluded that QST showed subtle sensory abnormalities in patients with TN despite not being detected in routine clinical examination.  They stated that these findings may provide a basis for further research on the development of TN and also on improvement after treatment; and more data are needed on the correlation of such findings with the length of history of TN and with changes of the morphology of the trigeminal nerve.

Quantitative Sensory Testing / Current Perception Threshold Testing for Restless Legs Syndrome/Willis-Ekbom Disease

Cho and colleagues (2018) stated that restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sensorimotor neurological disorder, and it is especially aggravated at night.  These researchers examined the diurnal sensory dysfunction in primary RLS/WED using the CPT test, compared to healthy controls.  A total of 30 primary RLS/WED subjects and 30 healthy controls were enrolled.  The severity of RLS/WED and sleep problems were evaluated in all subjects.  Peripheral polyneuropathy was excluded through neurological examination and nerve conduction study.  These investigators used the Neurometer system for the CPT test and applied 3 different parameters (2,000 Hz, 250 Hz, and 5 Hz) to stimulate both big toes.  The CPT test was performed twice, once during the asymptomatic daytime period and again in the evening, when the patients were symptomatic.  The mean ages of the RLS/WED group and controls were 50.5 ± 11.7 (22; 73.3 % women), and 46.3 ± 11.4 (24; 80.0 % women), respectively.  The mean international RLS/WED study group severity scale score was 28.6 ± 4.25.  There was no significant difference in the CPTs between the RLS/WED patients and controls in daytime.  However, the RLS/WED patients had lower mean CPT measurements for all 3 stimulation protocols in the evening (2,000 Hz: 393.2 ± 93.7 versus 430.8 ± 79.6, 250 Hz: 172.0 ± 48.4 versus 198.5 ± 38.2, and 5 Hz: 98.0 ± 34.1 versus 124.6 ± 31.3), while the healthy controls showed no difference.  The authors concluded that RLS patients showed a lower CPT in the evening.  The diurnal variation of hyperalgesia in RLS/WED patients indicated a central (circadian) sensory processing disturbance rather than a peripheral disturbance.  These preliminary findings need to be validated by well-designed studies.

Furthermore, an UpToDate review on “”Clinical features and diagnosis of restless legs syndrome/Willis-Ekbom disease and periodic limb movement disorder in adults (Ondo, 2018) does not mention quantitative sensory testing / current perception threshold testing as a diagnostic tool.

Quantitative Sensory Testing for Management of Oxaliplatin-Induced Peripheral Neuropathy

Delmotte and co-workers (2018) carried out a 2-year prospective study to better understand how QST could help the clinician in the management of oxaliplatin-induced peripheral neuropathy (PN) in terms of earlier and more reliable detection.  Thermal sensory assessment, tactile sensory assessment, neuropathic pain assessment and adverse events (AEs) gradation (NCI-CTC) were performed during treatment and 6 months following  completion of treatment.  A total of 35 patients were enrolled and followed-up during 1 year.  Cold and warm detection thresholds were higher 6 months after treatment completion than at enrollment.  Mechanical detection thresholds didn't change significantly.  Neurotoxicity was mostly grade-1, only 18 % grade-2 and no grade-3.  Grade-2 patients received lower oxaliplatin cumulative dose than grade-1, which revealed effective dose adaptation and grade-2 patients were more likely to develop painful PN.  The authors concluded that thermal thresholds impairment emerged too late to help the clinician in the prophylaxis of PN.  Management of oxaliplatin-treatment based on NCI-CTC, as currently recommended, remained the best way to detect PN and ensure treatment adaptation.

Quantitative Sensory Testing for Management of Peripheral Neuropathy in Head and Neck Cancer

Roldan and associates (2018) noted that chemotherapy-induced PN (CIPN) is a common and chronic complication associated with cancer treatment.  Prior investigations have demonstrated the presence of sub-clinical PN in patients with colorectal cancer (CRC) even before the patients had received chemotherapy.  In a retrospective analysis, these investigators examined sub-clinical PN of the upper limbs in patients with squamous cell carcinoma of the head and neck (HNSCC), which developed before their exposure to neurotoxic anticancer agents.  With the use of the authors’ QST data bank, they retrospectively assessed the afferent fiber function of 25 patients with HNSCC before they had received chemotherapy (the patient group) and compared the findings with those from 23 healthy control patients.  Skin temperature, sensorimotor function, sharpness detection, thermal detection, and touch detection (using both von Frey monofilaments and the Bumps detection test) were measured.  Touch thresholds were statistically higher in the patient group than in the healthy volunteer group at the palm (mean [± SD], 0.54 g [± 0.07 g] and 0.27 g [± 0.05 g], respectively [p < 0.01]) and at the forearm (0.74 g [± 0.12 g] and 0.41 g [± 0.08 g] [p < 0.05]).  There was also a clear deficit in touch sensation as indicated by a Bumps detection threshold in patients of 6.5 µm ± 0.8 µm and in controls of 3.7 µm ± 0.5 µm.  This yielded an elevation in threshold to 165 % in the patients relative to that of the control volunteers. The grooved pegboard test showed delayed completion times for patients compared with controls, with differences of 18.65 seconds in the dominant hand and of 23.36 seconds in the non-dominant hand.  The sharpness detection thresholds did not differ between patients and volunteers.  The authors concluded that patients with HNSCC were found to have deficits in sensory function before undergoing treatment, suggesting that cancer itself altered peripheral nerve function and may contribute to the development of CIPN.  These results confirmed the sensitivity of the Bumps detection test and highlighted its potential role in early detection of PN, especially in cancer patients for whom chemotherapies associated with CIPN have been prescribed.

The authors stated that the drawbacks of this study included inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study.  In addition, based on available information, these investigators did not find an objective parameter able to correlate the QST findings with pre-pain levels.

Quantitative Sensory Testing / Current Perception Threshold Testing for Management of Chronic Pain Following Lower Extremity Fracture

Griffioen and colleagues (2018) stated that chronic pain is a significant problem for patients with lower extremity injuries.  While pain hypersensitivity has been identified in many chronic pain conditions, it is not known whether patients with chronic pain following lower extremity fracture report pain hypersensitivity in the injured leg.  These researchers quantified and compared peripheral somatosensory function and sensory nerve activation thresholds in persons with chronic pain following lower extremity fractures with a cohort of persons with no history of lower extremity fractures.  This was a cross-sectional study where QST and CPT testing were conducted on the injured and non-injured legs of cases and both legs of controls.  A total of 14 cases and 28 controls participated in the study.  Mean time since injury at the time of testing for cases was 22.3 months (standard deviation = 12.1).  The warmth detection threshold (p =0 .024) and nerve activation thresholds at 2,000-Hz (p < 0.001) and 250-Hz (p = 0.002), respectively, were significantly higher in cases compared to controls.  The authors concluded that the findings of this study suggested that patients with chronic pain following lower extremity fractures may experience hypoesthesia in the injured leg, which contrasted with the finding of hyperesthesia previously observed in other chronic pain conditions; but was in accordance with patients with nerve injuries and surgeries.  This was the first study to examine peripheral sensory nerve function at the site of injury in patients with chronic pain following lower extremity fractures using QST and CPT testing.  These researchers stated that it is important that future studies examining chronic pain following traumatic lower extremity fractures use both QST and CPT because CPT reflects the function of afferent fibers, while QST reflects the function of both skin receptors and afferent fibers.  Research contributing to the understanding of the underlying mechanisms associated with chronic pain following lower extremity fractures has the potential to markedly improve patient quality of life (QOL), aid in the development of trauma-specific practice guidelines, and decrease health-care costs associated with chronic pain.

The authors stated that this study had several drawbacks.  First, the sample size was small (n = 14 cases of fractures).  Second, these investigators performed the testing in subjects at different time-points following injury.  Readers should interpret the CPT results with caution, as several subjects had inconsistent responses resulting in a small sample size.  Third, some of the subjects took medication for their pain, which could have affected the results.  Furthermore, these researchers had no information on the extent of nerve damage associated with the injuries; thus, it was possible that some of the subjects might have had sub-clinical nerve injuries.  The authors tried to lessen the effects of this limitation by waiting to test patients until at least 6 months after injury, when one would expect the majority of subtle nerve injuries to have resolved.  These researchers stated that a future longitudinal study in which investigators perform QST, CPT, and nerve biopsies at several time-points following injury would provide information regarding how sensory function changes as the injury heals.  For all future studies, examining data from both QST and CPT testing, as the authors did in the present study, would increase the reliability of results.

Quantitative Sensory Testing for Management of Pain in Autism Spectrum Disorders

Vaughan and associates (2020) noted that sensory abnormalities in autism has been noted clinically, with pain insensitivity as a specified diagnostic criterion.  However, there is limited research using psychophysically robust techniques.  In this study, 13 adults with ASD and 13 matched controls completed an established QST battery, supplemented with measures of pain tolerance and central modulation.  The ASD group showed higher thresholds for light touch detection and mechanical pain.  Notably, the ASD group had a greater range of extreme scores (the number of z-scores outside of the 95 % CI: greater than 2), dynamic mechanical allodynia and paradoxical heat sensation; phenomena not typically observed in neuro-typical individuals.  The authors concluded that these data supported the need for research examining central mechanisms for pain in ASD and greater consideration of individual difference.

Quantitative Sensory Testing for Evaluation of Chronic Itch

van Laarhoven and colleagues (2019) noted that patients suffering from chronic itch exhibit signs of peripheral and central sensitization.  This has been linked to parallel neuroplastic sensitization processes.  However, for chronic itch, sensitization has not yet been systematically assessed, studied, and hence validated.  This review (Prospero CRD42016043002) summarized and meta-analytically examined if sensory aberrations including sensitization for itch occur in chronic itch.  PubMed, Embase, and Cochrane Library were searched for studies examining somatosensory sensitivity assessment by QST stimuli, including experimental cutaneous chemical pruritic provocations, in patients with chronic itch from skin/neurological conditions and compared with healthy controls.  Outcomes were extracted for lesional and non-lesional skin, and risk of biases were assessed.  Meta-analyses were carried out when sufficient quantitative data were available.  Of 4,667 identified articles, 46 were included and 25 were eligible for meta-analyses.  Patients (66 % atopic dermatitis [AD]) were found more sensitive than the controls to histamine-evoked itch in lesional skin (standardized mean difference [SMD]: 0.66 CI: 0.16 to 1.15), but not non-lesionally (SMD: -0.26 [CI: -0.58 to 0.06]).  Cowhage did not evoke more itch in non-lesional skin of patients as compared to the controls (SMD: 0.38 [CI: -0.04 to 0.81]).  For numerous other chemical provocations as well as for mechanical, thermal, and electrical stimulation paradigms, results were ambiguous or based on few studies.  The authors concluded that patients with chronic itch are only robustly sensitized to various chemical pruritic stimuli when applied lesionally.  These researchers stated that more studies on somatosensory aberrations in chronic itch conditions other than AD are needed to establish whether sensitization is robustly present across chronic itch conditions.

Quantitative Sensory Testing for Evaluation of Pain Intensity or Disability in Chronic Pain

Schoth and colleagues (2019) presented the protocol for a systematic review and meta-analysis on “Association between quantitative sensory testing and pain or disability in pediatric chronic pain”.  This protocol described the objective and methods of a systematic review of the association between QST measures and pain intensity or disability in pediatric chronic pain (PCP).  The review will also examine if the relationship strength is moderated by variables related to the QST method and pain condition; the use of QST in PCP (modalities, outcome measures and anatomical test sites as well as differentiating between pain mechanisms (e.g., neuropathic versus nociceptive) and in selecting analgesics); the reliability of QST across the pediatric age range; the ability of QST to differentiate patients with chronic pain from healthy controls; and differences between anatomical test sites.  Medline, PsycINFO, CINHAL, Web of Science, Scopus, Cochrane Library and OpenGrey will be searched.  English language studies will be eligible if they recruit a sample aged 6 to 24 (inclusive) with chronic pain, including primary and secondary pain; apply at least one of the following QST modalities: chemical, electrical, mechanical (subgroups include pressure, punctate/brush and vibratory) or thermal stimulus to measure perception of noxious or innocuous stimuli applied to skin, muscle or joint; use a testing protocol to control for stimulus properties: modality, anatomical site, intensity, duration and sequence.  Following title and abstract screening, the full texts of relevant records will be independently assessed by 2 reviewers.  For eligible studies, 1 reviewer will extract study characteristics and data, and another will check for accuracy.  Both will undertake independent quality assessments using the Appraisal Tool for Cross-Sectional Studies.  A qualitative synthesis will be presented with discussion centered around different QST modalities.  Where eligible data permit, meta-analyses will be performed separately for different QST modalities using comprehensive meta-analysis.  Review findings will be reported in a peer-reviewed journal and presented at conferences.

Quantitative Sensory Testing for Evaluation of Tumor-Related Cancer Pain

Martland and colleagues (2020) reviewed the evidence on the use of QST in the assessment of pain in people with cancer and described which QST parameters consistently demonstrated abnormal sensory processing in patients with cancer pain.  Medline, Embase, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain.  Search strategies were based on the terms "quantitative sensory testing", "cancer", "pain", "cancer pain" and "assessment".  Data-bases were searched from inception to January 2019.  Data were extracted and synthesized narratively, structured around the different QST modalities and sub-grouped by cancer pain etiology (tumor- or treatment-related pain).  Searches identified 286 records of which 18 met the eligibility criteria for inclusion; 3 studies included patients with tumor-related pain, and 15 studies included patients with pain from chemotherapy-induced peripheral neuropathy (CIPN).  Across all studies, 50 % (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44 % (8/18) reported abnormal mechanical detection thresholds using von-Frey filaments and 39 % (7/18) found abnormal pinprick thresholds.  Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in 1/3 of included studies.  The authors concluded that this systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli.  However, these findings were based primarily on studies of CIPN and data on tumor-related pain are lacking, warranting further research.

Quantitative Sensory Testing for Diagnosis of Small Fiber Neuropathy in Postural Orthostatic Tachycardia Syndrome

In a retrospective study, Billig and colleagues (2020) examined the somatosensory profile and prediction of histologic small fiber neuropathy (SFN) in postural orthostatic tachycardia syndrome (POTS) using QST as a standardized non-invasive test.  Full data sets from 30 patients (age of 34.03 ± 10.82 years, n = 6 males), including results of autonomic function testing, norepinephrine values, skin biopsy, and QST, were retrospectively analyzed.  The QST data were compared with healthy controls (HCs) (age of 34.20 ± 10.5 years, n = 6 males, t-test: 0.95).  The evaluation of all QST parameters in POTS compared with HCs yielded differences in all thermal parameters (cold detection threshold: p < 0.05, warm detection threshold: p < 0.001, thermal sensory limen: p < 0.001, cold pain threshold: p < 0.05, and heat pain threshold: p < 0.001) and in paradoxical heat sensations (p < 0.05).  Differences in non-painful stimuli (mechanical detection threshold: p < 0.05, and vibration detection threshold: p < 0.001) were also detected.  All patients who had clinical signs of SFN in combination with impairment of small fibers in QST also had SFN on skin biopsy.  The authors concluded that these findings suggested that a non-region-specific SFN in POTS compared with controls could be detected by non-invasive QST that predicts histologic small fiber pathology.  Moreover, these researchers stated that the main drawbacks of this study were its retrospective design and small sample size (n = 30); therefore, limiting the generalization of these data.  Furthermore, possible effects of drug treatment of POTS on small fibers were not considered.  They stated that large, prospective trials are needed to examine if QST is suitable for the non-invasive diagnosis of SFN in POTS as it might predict histologic SFN.

Furthermore, an UpToDate review on “Postural tachycardia syndrome” (Kaufmann and Freeman, 2021) does not mention quantitative sensory testing as a management / therapeutic option.

Quantitative Sensory Testing for Prediction of Post-Operative Pain

Sangesland and colleagues (2017) stated that pain following surgery is not uncommon with 30 % of patients reporting moderate-to-severe post-operative pain.  Early identification of patients susceptible to post-operative pain may be a step forward towards individualized pain medicine providing a basis for improved clinical management via therapeutic strategies targeting relevant pain mechanisms in individual patient.  Assessment of pain processing by (QST before surgery has been proposed as a method to identify patients at risk for post-operative pain, although results have been conflicting.  Since the last systematic review, several studies examining the association between post-operative pain and more dynamic measures of pain processing like temporal summation of pain (TSP) and conditioned pain modulation (CPM) have been carried out.  In a systematic review based on the PRISMA guidelines, these investigators examined if assessment of experimental pain processing including measures of central pain mechanisms before surgery was associated with pain intensity following surgery.  They carried out systematic database searches in PubMed and Embase with the following search components: QST, association, and post-operative pain, for studies that evaluated the association between QST and pain after surgery.  Two authors independently reviewed all titles and abstracts to examine their relevance for inclusion.  Studies were included if QST was performed prior to surgery; pain was assessed after surgery; and the association between QST and pain after surgery was investigated.  A total of 44 unique studies were identified, with 30 studies on 2,738 subjects met inclusion criteria.  The methodological quality of the included studies was examined; and data extraction included study population, type of surgery, QST variables, clinical pain outcome measure and main result.  Most studies showed moderate-to-high risk of bias.  Type of surgery examined include 7 studies on total knee replacement (TKR), 5 studies on Caesarean section, 4 studies on thoracic surgery, 2 studies on herniotomy, 2 studies on hysterectomy/myomectomy, 1 study on tubal ligation, 1 study on gynecologic laparoscopy, 1 study on arthroscopic knee surgery, 1 study on shoulder surgery, 1 study on disc herniation surgery, 1 study on cholecystectomy, 1 study on percutaneous nephrolithotomy, 1 study on molar surgery, 1 study on abdominal surgery, and 1 study on TKR and total hip replacement.  The majority of the pre-operative QST variables showed no consistent association with pain intensity following surgery.  Thermal heat pain above the pain threshold and temporal summation of pressure pain were the QST variables, which showed the most consistent association with acute or chronic pain after surgery.  The authors concluded that QST before surgery did not consistently predict pain following surgery.  These researchers stated that high quality studies examining the presence of different QST variables in combination or along with other pain-related psychosocial factors are needed to confirm the clinical relevance of QST prior to surgery.

van Helmond and associates (2020) stated that persistent post-surgical pain (PPSP) is a common complication of surgery that significantly affects QOL.  A better understanding of which patients are likely to develop PPSP would help to identify when peri-operative and post-operative pain management may require specific attention.  Quantitative sensory testing of a patient's pre-operative pain perception is associated with acute post-operative pain, and acute post-operative pain is a risk factor for PPSP.  The direct association between pre-operative QST and PPSP has not been examined to-date.  In a systematic review, these researchers evaluated the relationship of pre-operative QST to PPSP.  They searched databases with components related to pre-operative QST; association testing; and PPSP; 2 authors reviewed all titles and abstracts for inclusion.  Inclusion criteria included QST performed before surgery; PPSP evaluated greater than or equal to 3 months post-operatively; and the association between QST measures and PPSP.  The search retrieved 905 articles; 24 studies with 2,732 subjects met inclusion criteria.  Most studies (22/24) had moderate-to-high risk of bias in multiple quality domains; 14 (58 %) studies reported a significant association between pre-operative QST and PPSP.  Pre-operative temporal summation of pain (4 studies), conditioned pain modulation (3 studies), and pressure pain threshold (3 studies) showed the most frequent association with PPSP.  The strength of the association between pre-operative QST and PPSP varied from weak-to-strong.  The authors concluded that pre-operative QST was variably associated with PPSP; and measurements related to central processing of pain may be most consistently associated with PPSP.

Petersen and co-workers (2021) noted that studies have suggested that QST might hold a predictive value for the development of chronic post-operative pain and the response to pharmacological interventions.  These investigators reviewed the current evidence on the predictive value of QST for chronic post-operative pain and the effect of pharmacological interventions.  The main outcome measures were post-treatment pain intensity, pain relief, presence of moderate-to-severe post-operative pain, responders of 3 0% and 50 % pain relief, or validated questionnaires on pain and disability.  These researchers carried out a systematic search of Medline and Embase, which yielded 25 studies on surgical interventions and 11 on pharmacological interventions; 17 surgical and 11 pharmacological studies reported an association between pre-operative or pre-treatment QST and chronic post-operative pain or analgesic effect.  The most commonly assessed QST modalities were pressure stimuli (17 studies), TSP (14 studies), and CPM (16 studies).  Of those, the dynamic QST parameters TSP (50 %) and CPM (44 %) were most frequently associated with chronic post-operative pain and analgesic effects.  A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found.  Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses.  The authors concluded that the findings of this systematic review revealed that TSP and CPM showed the most consistent predictive values for chronic post-operative pain and analgesic effect; however, the heterogeneous methodologies reduced the generalizability and hence call for methodological guidelines.

Braun and colleagues (2021) examined the relevance of QST in light of acute and chronic post-operative pain and associated challenges.  These investigators stated that predicting the occurrence of acute and chronic post-operative pain with QST could help identify patients at risk and allows proactive preventive management.  Generally, central QST testing, such as TSP and CPM, appear to be the most promising modalities for reliable prediction of post-operative pain by QST.  Overall, QST testing has the best predictive value in patients undergoing orthopedic procedures.  The authors concluded that current evidence underlines the potential of pre-operative QST to predict post-operative pain in patients undergoing elective surgery.  These researchers stated that future high-quality studies combining central QST procedures, such as TPS and CPM, can help advancing traditional pain therapy towards personalized peri-operative pain medicine.  These projects should include study designs that combine non-QST-associated parameters such as anxiety, pre-existing pre-operative pain, or pain catastrophizing; and QST need to be standardized in order to reduce potential bias.  They noted that comprehensive pre-operative QST testing of patients undergoing elective surgery might become a milestone in personalized peri-operative pain medicine, with the potential to reduce the increasing burden of pain and improve QOL.

The authors stated that a major problem of QST research is the heterogeneity of the data and the complexity of the studies.  Several QST protocols combined different test settings and modalities.  Timing of the pre-operative QST, for example, varied widely or was not reported, although the timing may be essential.  The testing itself does not show high consistency; however, the findings may change over time in an individual.  Good reproducibility of QST in healthy patients may last just days or weeks.  Not only duration of testing but also location may have an impact.  For example, in orthopedic surgery, the use of the QST may show different results on the surgical and contralateral sides.  Many studies included a high rate of bias.  It has been suggested that study protocols should be harmonized for a better understanding of QST; or making them shorter and easier for clinical use.  Most of the included studies had at least moderate or even high bias.  This may have led to an over-estimation of the correlation in the studies with a higher risk of bias; 92 % of the studies examined by van Helmond et al (2020) had a moderate or high risk of bias; only Petersen et al (2021) classified studies as low-to-moderate risk.  Sangesland et al (2017) classified only 7 of 30 studies as low bias (4 of them showed positive results for QST).  In addition, studies with a high risk of bias often have sub-optimal predictive value (Petersen et al, 2021).

Paredes and colleagues (2022) stated that QST can be useful to identify high-risk patients for the development of chronic post-surgical pain.  In a systematic review, these investigators examined if pre-surgical sensory sensitivity measured using QST is associated with acute and chronic post-surgical pain following total joint arthroplasty.  They carried out a systematic search in September 2020 in PubMed, Embase, Web of Science, and Scopus, using terms related to total joint arthroplasty and QST.  Prospective studies were included if they reported an association between pre-surgical QST and post-surgical pain in adults with osteoarthritis (OA) undergoing primary unilateral total joint arthroplasty.  From a total of 2,994 identified studies, 18 met the inclusion criteria (1,869 patients).  Total knee arthroplasty (TKA) was the most common surgery (16 studies), and pressure pain threshold was the most common test (11 studies), followed by dynamic measures (9 studies).  Post-surgical pain was examined at acute (5 studies), subacute (2 studies), and chronic (13 studies) time-points.  Risk of bias was evaluated using the Quality in Prognosis Studies tool and examined as low-to-moderate in most domains.  A total of 14 studies reported at least 1 statistically significant association between QST and pain (acute: 4 studies, subacute: 1 study, and chronic: 9 studies).  Pressure pain threshold was associated with post-surgical pain in 6 studies (of 11, 55 %), heat pain threshold in 2 studies (of 6, 33 %), conditioned pain modulation in 1 study (of 6, 17 %), and temporal summation of pain in 5 studies (of 8, 63 %).  The authors concluded that the predictive role of pre-surgical QST for post-arthroplasty pain remains unclear, mainly because of heterogeneous methodologies and inconsistent findings.

Quantitative Sensory Testing for Evaluation of Fibromyalgia Pain

Bertwick and colleagues (2021) stated that the role of temperature in fibromyalgia syndrome (FMS) pain has not been examined systematically.  In a systematic review, these investigators examined the influences of temperature on pain in FMS, from meteorological and QST studies.  This review followed PRISMA guidance.  Databases examined included Medline (via Ovid), Embase, PubMed, Web of Science, ScienceDirect, CINAHL, and ProQuest (February 20).  Exclusion criteria included age of less than 18 years, animal studies, non-English, and non-controlled articles.   Total of 13 studies pertaining to ambient temperature and FMS pain were identified; 9 of these found no uniform relationship.  A total of 35 QST studies were identified, 17 of which assessed cold pain thresholds.  All studies showed numerically reduced cold pain thresholds in patients, ranging from 10.9° C to 26.3° C versus 5.9° C to 13.5° C in controls; this was statistically significant in 14/17.  Other thermal thresholds were often abnormal.  The authors concluded that the available literature provided consistent evidence for an abnormal sensitization of FMS patients' temperature-sensation systems.  Moreover, these researchers stated that further investigation is needed to examine factors that determine why a subgroup of patients perceive low ambient temperatures as painful, and to characterize that group.  These investigators stated that FMS patients often report increased pain with changes in ambient temperature; even disabling, extreme temperature sensitivity in winter.  Understanding this phenomenon may aid clinicians in providing reassurance and advice to patients and may guide research into the everyday impact of such hypersensitivity, while directing future work into the pathophysiology of FMS.

Quantitative Sensory Testing for Evaluation of Temporal Changes in Pain Processing Following Whiplash Injury to Identify the Risk for Chronification

Bontinck and colleagues (2022) noted that after whiplash injury, some patients develop chronic whiplash-associated disorders.  The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases.  In a systematic review, these investigators examined temporal changes in pain processing, measured by QST.  They searched 3 electronic databases (Medline, Embase, and Web of Science) for articles meeting the eligibility requirements.  Risk of bias was evaluated using a modified Newcastle-Ottawa Scale.  The 12 included studies presented moderate-to-good methodological quality.  These studies showed altered pain processing within the 1st month after injury and normalization within 3 months in 59 % to 78 % of the patients.  After 3 months, recovery stagnates during the following years.  Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients.  The authors concluded that differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase.  Early screening for signs of altered pain processing can identify patients with high risk for chronification.  These insights in temporal changes showed the importance of rehabilitation in the acute phase.  These researchers stated that future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification.

Quantitative Sensory Testing for Evaluation of Women After Surgery for Breast Cancer

Dams et al (2021) stated that QST is a non-invasive technique to examine functioning of the somatosensory system.  In many women surgically treated for breast cancer (BC), somatosensory functioning is disturbed with high prevalence of sensory loss and/or pain.  In a systematic review were, these investigators summarized the evidence on QST methods as well as the results within women surgically treated for BC (patients and survivors); compared QST results between women surgically treated for BC with and without pain; and compared the results between women surgically treated for BC and women without history of BC.  They carried out a systematic literature search up to February 2020 . Included studies had to report on QST methods (mechanical or thermal detection-pain thresholds, pressure pain thresholds [PPT], TS, or CPM) in women over 18 years with-without pain, who had undergone unilateral surgery for BC.  A total of 28 studies were included.  Discrepancies in QST methods were greatest for TS and CPM.  A local disturbance in thermal detection and an increased pain facilitation were found in BC survivors with pain in the surgical area.  BC survivors with upper limb pain had significantly lower PPT at the surgical area and PPT were also significantly lower compared with women without history of BC, at affected and non-affected sides for both local and remote body regions.  The authors concluded that standardized QST incorporating assessments of CPM is needed to draw conclusions regarding neurobiological mechanisms of pain and somatosensory disturbances after surgical treatment for BC and to enhance mechanism-based management of these sequelae.

Dams et al (2022) QST are non-invasive psychophysical assessment techniques to evaluate functioning of the somatosensory nervous system.  Despite the importance of reliability for correct use of QST results in research and clinical practice, the relative and absolute intra-and inter-rater reliability of a comprehensive QST protocol to examine the functioning of both peripheral and central somatosensory nervous system in a BC population, has not yet been investigated.  A total of 30 women at least 6 months after unilateral BC surgery were included in this trial.  The protocol included 9 static and dynamic QST methods (mechanical detection-pain thresholds [DPT], thermal DPT for heat and cold, PPT, TS and CPM) carried out in the surgical area and more distant regions.  Absolute and relative intra (60-min interval) and inter-rater (1-week interval) reliability was examined using intra-class correlation coefficients (ICC), standard error (SE) of measurement and Bland-Altman plots.  A moderate-to-excellent relative intra- and inter-rater reliability was found for the evaluation of mechanical thresholds, PPT and TS.  Reliability of the CPM paradigm was considered weak.  Systematic bias between raters was noticed for detection of mechanical and cold stimuli at the non-affected trunk and CPM.  The authors concluded that except for the evaluation of CPM, the QST protocol was found suitable for identifying differences between subjects (relative reliability) and individual follow-up after BC surgery (limited systematic bias) during a 1-week timeframe.  Moreover, these researchers stated that additional research is needed to determine measurement properties that influence CPM test stability to establish a more reliable CPM test paradigm.

Quantitative Sensory Testing for Evaluation of Chronic Pelvic Pain

Coxon et al (2023) noted that chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically.  This trail, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full QST paradigm to profile women (n = 85) with and without CPP (endometriosis or bladder pain specifically).  These investigators employed the foot as a control site and abdomen as the test site.  Across 5 diagnostically determined subgroups, these researchers found features that are common across different etiologies (e.g., gain of function in PPT when assessing responses from the lower abdomen or pelvis (referred pain site).  However, disease-specific phenotypes were also identified (e.g., greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups).  The most common QST sensory phenotype was mechanical hyperalgesia (greater than 50 % across all the groups).  A "healthy” sensory phenotype was observed in less than 7 % of CPP participants.  Specific QST measures correlated with sensory symptoms assessed by the painDETECT questionnaire (pressure-evoked pain [painDETECT] and PPT [QST] [ r = 0.47, p < 0.001]; mechanical hyperalgesia (painDETECT), and mechanical pain sensitivity [MPS from QST] [ r = 0.38, p = 0.009]).  The authors concluded that this study showed significant changes of somatosensory function in women with CPP, with 6.8 % showing a “healthy” sensory profile.  Specific sensory alterations were present across different underlying pathologies, whereas others were disease-specific.  These investigators stated that these findings suggested that there is central sensitization to deep and cutaneous inputs in women with CPP, in addition to a variety of alterations in peripheral nerve function.  The data showed a moderate correlation between QST measures and relevant descriptors from painDETECT, suggesting painDETECT may have utility for phenotyping CPP patients in specific settings.  These researchers stated that understanding somatosensory processing may be helpful for phenotyping CPP patients; and stratification methods such as these may in future guide personalized pain management, and therefore, should be considered when designing clinical trials.

The authors stated that his study had several drawbacks.  First, attempts were made to ensure consistency of data by using the same equipment at all 3 sites and training all personnel together in data collection methods.  Although the overall sample size was comparable with other QST studies, when divided into clinical subgroups especially the PP group was too small to meaningfully interpret results.  Where appropriate, comparisons were made between those with and without endometriosis and those with and without bladder pain.  Second, these investigators could not exclude that some of the differences they found were based in site differences of this multi-center study.  This was based in the respective center's expertise and clinical focus.  A future study should aim to include recruiting at centers covering all groups equally.  Third, the lower abdomen or pelvis test site was selected as the most clinically meaningful area as this is often the referred pain site in CPP patients, however, there is no published reference QST data from this site.  Therefore, these researchers employed published QST data from the trunk area.  The study compared patient data with a control group (CON), and data were z-transformed using the trunk reference data.  These investigators did not consider it appropriate to use the control group as reference data for z-transformation as the sample size was not large enough and the spread of ages was relatively limited.

Kmiecik et al (2023) stated that multi-modal hypersensitivity (MMH), derived from QST, denotes greater sensitivity across multiple sensory modalities (e.g., light, sound, temperature, pressure), and is associated with the development of chronic pain.  However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multi-modal sensory testing, or limited follow-up.  These investigators carried out multi-modal sensory testing on an observational cohort of 200 reproductive-aged women, including those at elevated risk for CPP conditions and pain-free controls.  Multi-modal sensory testing included visual, auditory, and bodily pressure, pelvic pressure, thermal, and bladder pain testing.  Self-reported pelvic pain was examined over 4 years.  A principal component analysis of sensory testing measures resulted in 3 orthogonal factors that explained 43 % of the variance: MMH, pressure pain stimulus response, and bladder hyper-sensitivity.  The MMH and bladder hyper-sensitivity factors correlated with baseline self-reported menstrual pain, genito-urinary symptoms, depression, anxiety, and health.  Over time, MMH increasingly predicted pelvic pain and was the only component to predict outcome 4 years later, even when adjusted for baseline pelvic pain.  Multi-modal hyper-sensitivity was a better predictor of pelvic pain outcome than a questionnaire-based assessment of generalized sensory sensitivity.  The authors concluded that these findings suggested that MMHs overarching neural mechanisms conveyed more substantial long-term risk for pelvic pain than variation in individual sensory modalities.  These researchers stated that further investigations on the modifiability of MMH could inform future treatment developments in chronic pain.

Quantitative Sensory Testing for Evaluation of POEMS Syndrome and Lumbar Radiculopathy

Nygaard and Mellgren (1998) stated that results from experimental and clinical studies indicated that chronic compression of lumbar nerve roots affects the large myelinated nerve fibers.  The majority of nerve fibers involved in the sensation of pain, however, are small afferent nerve fibers.  Thus, it was of interest to study the effect of compression on large and small sensory afferent channels.  Several investigators have elucidated the biochemical interaction between disc tissue and nerve roots.  Chemical substances in the epidural space can reach the nerve fibers in nerve roots at the same or neighboring lumbar segments.  In this manner, fibers not involved in the mechanical compression may be affected.  These researchers examined the function of sensory nerve fibers in patients with lumbar radiculopathy and in control individuals using quantitative sensory testing (QST).  They examined the effect of lumbar nerve root compression on different populations of nerve fibers and explored the function of sensory nerve fibers in neighboring nerve roots not involved in the mechanical compression.  The small nerve fibers were studied using tests for thermal thresholds (thermotest), and the large myelinated fibers were studied by vibrametry.  A total of 42 patients were examined in the symptomatic and the asymptomatic leg, and the results were compared with those of 21 healthy individuals.  The thresholds of cold, warmth, and vibration were significantly increased in the dermatome of the compressed nerve root, indicating that large and small sensory nerve fibers were affected.  Furthermore, the thresholds were significantly increased in the neighboring dermatomes in the symptomatic and the asymptomatic leg.  The authors concluded that large and small sensory afferent nerve fibers were affected in lumbar radiculopathy.  The increase in sensation thresholds in the ipsilateral neighboring dermatome and in the dermatomes in the asymptomatic leg indicated that adjacent nerve roots were involved in the pathophysiology of sciatica in patients with lumbar disc herniation.

Tampin et al (2020) aimed to establish the somatosensory profile of patients with lumbar radiculopathy at pre-and post-microdiscectomy and examined any association between pre-surgical QST parameters and post-surgical clinical outcomes.  These researchers carried out standardized QST protocol in 53 patients (mean age of 38 ± 11 years, 26 females) with unilateral L5/S1 radiculopathy in the main pain area (MPA), affected dermatome and contralateral mirror sites and in age- and gender-,and body site-matched healthy controls.  Repeat measures at 3 months included QST, the Oswestry Disability Index (ODI) and numerous other clinical measures; at 12 months, only clinical measures were repeated.  A change of less than 30 % on the ODI was defined as “no clinically meaningful improvement”.  Patients showed a significant loss of function in their symptomatic leg both in the dermatome (thermal, mechanical, vibration detection p < 0.002), and MPA (thermal, mechanical, vibration detection, mechanical pain threshold, mechanical pain sensitivity p < 0.041) and increased cold sensitivity in the MPA (p < 0.001).  Pre-surgical altered QST parameters improved significantly post-surgery in the dermatome (p < 0.018) in the symptomatic leg and in the MPA (p < 0.010), except for thermal detection thresholds and cold sensitivity.  Clinical outcomes improved at 3 and 12 months (p < 0.001); 7 patients demonstrated less than 30 % change on the ODI at 12 months.  Baseline loss of function in mechanical detection in the MPA was associated with less than 30 % change on the ODI at 12 months (OR 2.63, 95 % CI: 1.09 to 6.37, p = 0.032).  The authors concluded that microdiscectomy resulted in improvements in affected somatosensory parameters and clinical outcomes.  Pre-surgical mechanical detection thresholds may be predictive of clinical outcome.  Moreover, these researchers stated that larger, high‐quality studies are needed to confirm these findings.

The authors stated that this study had several drawbacks.  First, these investigators chose the conservative cut‐off of less than 30 % change on the ODI (i.e., 10 points) as a clinically meaningful difference, others suggested a cut‐off of 20 points to ensure meaningful change following surgery.  This suggested cut‐off was not feasible as 36 (68 %) of the patients scored less than 20 points at baseline (i.e., creating a potential floor effect).  However, further analysis revealed that the findings in this trial were comparable using the patient global index of change (PGIC), which as an outcome measure, is independent of baseline values.  Second, the subgroups of patients with less than 30 % change on the ODI at 3 and 12 months were small, and the risk of a type II error could not be excluded.  Third, the use of pain medication may have influenced QST and clinical outcomes.  Fourth, surgery was carried out by the same surgeon, which limited generalizability of these findings.

Furthermore, an UpToDate review on “POEMS syndrome” (Dispenzieri, 2024) does not mention quantitative sensory testing as a management option.

Quantitative Sensory Testing for Evaluation of Shoulder Pain

Bilika et al (2023) noted that QST is a psycho-physical battery of various tests developed to quantify the subjects' self-reported sensory experience.  Although QST is employed for the clinical assessment of pain, standard evaluation protocols have not yet been established.  In a systematic review, these investigators examined the level of evidence for the psychometric properties of QST in healthy subjects and patients with shoulder pain.  A total of 8 databases were searched for peer-reviewed studies published until August 2021.  The methodological quality of studies was examined using the COSMIN check-list.  A total of 12 studies were included for qualitative synthesis, which included 3 different tests (PPT, CPM, and TS).  As the body of evidence consisted of studies of low methodological quality, the psychometric properties of PPT, CPM, and TS in healthy subjects and patients with shoulder pain were classified as unknown.  The authors concluded that the present study showed that the evidence level of the reliability and validity of the QST is at a very early stage, which meant that healthcare practitioners should be very careful when using QST in patient assessment and decision-making.  Moreover, these researchers stated that further studies are needed for the CPM and TS in patients with shoulder pain.

The authors stated that this study had several drawbacks including this systematic review included only published studies; thus, the findings may be over-estimated (publication bias).  However, this was an agreed decision in order to increase the internal validity of these findings, since grey literature has not undergone a peer-review process, and the deriving data and conclusions may be of doubtful quality.  In addition, the studies were evaluated only in English; therefore, limiting the total number of studies.

Assessment of Central Sensitization with Quantitative Sensory Testing in Inflammatory Rheumatic Diseases

Trouvin et al (2022) stated that the major therapeutic challenge in inflammatory rheumatic diseases is the persistence of pain despite good responses to specific therapies.  Central sensitization, which can be evaluated by psychophysical measurements, including QST, is a widely proposed mechanism for chronic pain.  In a systematic review, these researchers examined the available evidence addressing QST in inflammatory rheumatic diseases.  They searched PubMed and Embase for publications up to December 2021 concerning studies on QST focusing on pain thresholds, temporal summation (TS) and conditioned pain modulation (CPM), in adult patients with chronic inflammatory rheumatism (e.g., rheumatoid arthritis [RA], spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis [JIA]).  The exclusion criteria were reviews, inclusion of children and no reported pain threshold.  Data quality was examined with the National Institutes of Health (NIH) Quality Assessment tools.  These investigators identified 27 studies (18 controlled, 9 uncontrolled) including 1,875 patients with inflammatory rheumatic diseases and 795 controls.  A decrease in pressure pain threshold, in favor of allodynia, was found in 12 of 14 controlled studies on patients with RA and spondyloarthritis.  The results of other psychophysical tests, including TS and CPM, were inconsistent due to population heterogeneity and a lack of standardization of the patients' disease duration, activity and treatment.  The authors concluded that this review showed that pain in chronic inflammatory rheumatism was associated with pressure allodynia; however, given the heterogeneous quality and discrepant results of studies of other QST outcome measures, the hypothesis of central sensitization involvement in pain processing in these patients could not be confirmed.

Quantitative Sensory Testing for Identification of Pain Characteristics in Patients with Osteoarthritis

Arant et al (2022) outlined the most commonly used QSTs to identify pain sensitization.  These researchers examined cross-sectional associations between QST measures and osteoarthritis (OA) symptoms and severity, along with longitudinal associations between QST findings and response to surgical and non-surgical treatments for OA.  They carried out a search in PubMed for English language studies including “osteoarthritis” and “quantitative sensory testing” as search terms.  Studies that did not specifically address OA or QST were excluded.  Pressure Pain Threshold (PPT), CPM, and TS are the QST measures used most frequently to identify pain sensitization.  Findings indicated that patients with knee OA often exhibit lower PPT thresholds, inefficient CPM, and facilitated TS as compared with controls who do not have OA, supporting the discriminant validity of QST.  Pre-treatment QST has shown some success in identifying patients who experienced less pain relief from surgical and non-surgical treatments for knee OA.  Post-treatment QST has shown that sometimes PPT and CPM could normalize (PPT thresholds increase, and CPM becomes efficient) in patients for whom joint replacement was successful.  Recent studies indicated that QST measures were more closely associated with pain severity than OA radiographic severity, suggesting that sensitization may be a trait rather than a state.  The authors concluded that QST may have a role in identifying individuals who are susceptible to chronic pain and may offer an opportunity for personalized, more effective treatment of OA.  Moreover, these investigators stated that there is insufficient evidence to determine whether the normalization of QST measures was associated with pain improvement, or, similarly, whether lack of normalization was related to persistent pain.

Quantitative Sensory Testing for Acute musculoskeletal Pain Post-Surgery or Post-Injury

Li et al (2023) noted that QST is increasingly used in pediatric chronic pain; however, examination in youth with acute musculoskeletal (MSK) pain is limited.  These investigators examined the feasibility, reliability, and sources of variability of a brief QST protocol in 2 clinical samples of youth with acute MSK pain.  Subjects were 277 youth (mean age of 14.5 years, SD = 2.0, range of 11 to 18 years, 59 % female, 81 % non-Hispanic) across 3 geographic study sites who completed a QST protocol evaluating pressure and thermal pain sensitivity, TS of pain, and CPM 8 weeks after MSK surgery (n = 100) or within 4 weeks after an acute MSK injury (n = 177).  High feasibility was demonstrated by protocol completion rates ranging from 97.5 % to 100 % for each task, with 95.3 % of youth completing all tasks.  Reliability was high, with reliability coefficients of greater than 0.97 for 7 out of 8 QST parameters and minimal influence of examiner or participating site effects.  Younger youth had lower pressure and heat pain thresholds (11 to 12 versus 13 to 18 years, d = -0.80 to -0.56) and cold pain tolerance (d = -0.33).  Hispanic youth had higher pressure and heat pain thresholds (d = 0.37-0.45) and pain ratings for cold pain tolerance (d = 0.54) compared with non-Hispanic youth.  No significant differences were observed in QST values by sex or personal contextual factors at the time of assessment (momentary pain, menstrual period, use of pain medications).  The authors concluded that these findings showed feasibility of a brief QST protocol with youth with diverse acute MSK pain and these results provided initial support for the reliability of this QST protocol for multi-site research studies.

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References