Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus

Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility, and interpretation of results. A consensus meeting was convened by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) to formulate recommendations for conducting QST in clinical practice and research. Research studies have confirmed the utility of QST for the assessment and monitoring of somatosensory deficits, particularly in diabetic and small fiber neuropathies; the assessment of evoked pains (mechanical and thermal allodynia or hyperalgesia); and the diagnosis of sensory neuropathies. Promising applications include the assessment of evoked pains in large-scale clinical trials and the study of conditioned pain modulation. In clinical practice, we recommend the use QST for screening for small and large fiber neuropathies; monitoring of somatosensory deficits; and monitoring of evoked pains, allodynia, and hyperalgesia. QST is not recommended as a stand-alone test for the diagnosis of neuropathic pain. For the conduct of QST in healthy subjects and in patients, we recommend use of predefined standardized stimuli and instructions, validated algorithms of testing, and reference values corrected for anatomical site, age, and gender. Interpretation of results should always take into account the clinical context, and patients with language and cognitive difficulties, anxiety, or litigation should not be considered eligible for QST. When appropriate standards, as discussed here, are applied, QST can provide important and unique information about the functional status of somatosensory system, which would be complementary to already existing clinical methods.     

Different underlying pain mechanisms despite identical pain characteristics: a case report of a patient with spinal cord injury

Pain following spinal cord injury has been classified as nociceptive (musculoskeletal, visceral) or neuropathic (above, at, below level). There is no clear relation between the etiology and reported symptoms. Thus, due to different underlying mechanisms, the treatment is often ineffective. We report on a patient with spinal cord injury with neurological level of injury at T8 suffering from bilateral burning and prickling pain in the T9-11 dermatomes bilaterally (at-level pain), as well as diffusely in both legs from below the torso (below-level pain), accompanied by musculoskeletal low back pain. Bilateral comparison of quantitative sensory testing (QST) and skin biopsy revealed completely different findings in the dermatome T9 despite identical at-level pain characteristics. On the right side, QST revealed a normal sensory profile; the intraepidermal nerve fiber density (IENFD) was reduced, but not as severe as the contralateral side. On the left side there was a severe sensory loss with a stronger reduction of the IENDF, similar to the areas below the neurological level. These findings were significantly related to the treatment results. Pregabalin induced unilateral pain relief only in the area with remaining sensory function, whereas the left-sided at-level pain was unchanged. Thus, 2 different underlying mechanisms leading to bilaterally neuropathic pain with identical symptoms and with different treatment success were demonstrated in a single patient. The at-level pain in areas with remaining sensory function despite IENFD reduction could be relieved by pregabalin. Thus, in an individual case, QST may be helpful to better understand pain-generating mechanisms and to initiate successful treatment.     

Influence of pain reduction by transcutaneous electrical nerve stimulation (TENS) on somatosensory functions in patients with painful traumatic peripheral partial nerve injury

Following peripheral nerve injury sensory loss is taken as a sign of denervation. However, based on reports of improved sensitivity following relief of pain it has been suggested that a functional block produced by the activity in the nociceptive system itself may be responsible for at least part of the sensory aberrations. The aim was to examine if pain reduction by high‐frequency TENS influenced somatosensory functions in patients with long‐term unilateral painful traumatic peripheral partial nerve injury. Eighteen patients with spontaneous ongoing pain and a touch sensation in the innervation territory of the injured nervous structure of at least 5 on an intensity 11‐point Likert rating scale compared with contralaterally, participated. Before and following 80 Hz TENS with a stimulus intensity generating non‐painful paresthesiae in the painful areas during 30 min the pain intensity was rated on a numerical rating scale and bedside examination of somatosensory functions (BE) and quantitative sensory testing (QST) were performed in the same areas. Before and following TENS there was no difference in sensory functions between nine patients with ≥50% pain reduction and nine patients with a smaller or no reduction in pain. Compared to baseline, only minor TENS‐induced alterations in somatosensory functions were found at BE in conjunction with decreased sensitivity to light touch at QST (p < 0.01) in both groups alike. In conclusion ≥50% pain reduction by TENS did not alter sensory functions differentially compared to a smaller or no reduction in pain.     

Zertifizierungsrichtlinien für QST-Labore

Quantitative sensory testing (QST) is the standardized assessment of the somatosensory system comprising all sensory submodalities. In the German Research Network on Neuropathic Pain (DFNS), a QST-battery consisting of 13 parameters has been established and nationwide normative data have been collected. In contrast to conventional electrophysiology, QST allows detecting negative and positive sensory signs of both large and small fiber systems. However, as a subjective psychophysical method it is critically dependent on patients’ / healthy subjects’ cooperation thus strictly standardized protocols and instructions are needed to allow across laboratory comparisons. To facilitate more widespread use of QST, the German Pain Society (DGSS) and the DFNS have initiated a certification procedure for QST quality standards. Therefore, structural, procedural criteria and outcome parameters were establishd and are hereby presented. By maintaining high quality standards, the certification of QST is intended to contribute to a better understanding of the mechanisms behind neuropathic pain syndromes and thereby improve patient care as well as sensory assessment in clinical studies on the treatment of neuropathic pain syndromes.     

Lidocaine patch (5%) produces a selective, but incomplete block of Aδ and C fibers

Topical lidocaine (5%) leads to sufficient pain relief in only 29%-80% of treated patients, presumably by small-fiber block. The reasons for nonresponse are unclear; it may be due to different underlying pain mechanisms or partly insufficient anesthetic effect. Using quantitative sensory testing (QST) following the protocol of the DFNS (German Research Network on Neuropathic Pain), this study aims to assess the type and extent of somatosensory changes after lidocaine application in healthy volunteers. Twenty-six healthy volunteers underwent QST on the volar forearm, including thermal and mechanical detection and pain thresholds, twice before (for baseline retest reliability) and once after 6-hour simultaneous application with lidocaine patch 5% and contralateral placebo in a double-blinded manner. Pre and post differences of QST parameters were analyzed by paired t-test (Bonferroni-corrected alpha 0.0023). QST profiles did not change between the 2 baseline measurements and after the placebo application. Lidocaine application led to a significant change of only the small-fiber-associated thresholds (increase of thermal detection and mechanical pain thresholds, decrease of mechanical pain sensitivity). Tactile detection thresholds representing Aβ function remained unchanged. Interindividually, the extent of the small-fiber block varied widely (eg, thermal detection thresholds: in 54% of the subjects there were only minimal changes; in only 8% were there changes of >60% of the maximal achievable value). Topical lidocaine (5%) induces thermal hypoesthesia and pinprick hypoalgesia, suggesting an isolated but only partial block of Aδ and C fibers of unpredictable extent. Further studies must analyze the influencing factors and determine whether patients with poor analgesic effect, in particular, are those with insufficient small-fiber block.     

Patients initially diagnosed as 'warm' or 'cold' CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study

We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.     

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.     

Somatosensory abnormalities in atypical odontalgia: A case-control study

Somatosensory function in patients with persistent idiopathic types of orofacial pain like atypical odontalgia (AO) is not well described. This study tested the hypothesis that AO patients have significantly more somatosensory abnormalities than age- and sex-matched controls. Forty-six AO patients and 35 controls participated. Inclusion criteria for AO were pain in a region where a tooth had been endodontically or surgically treated, persistent pain >6 months, and lack of clinical and radiological findings. The examination included qualitative tests and a battery of intraoral quantitative sensory testing (QST). Most AO patients (85%) had qualitative somatosensory abnormality compared with few controls (14%). The most common qualitative abnormalities in AO patients were found with pin-prick 67.4%, cold 47.8%, and touch 46.5% compared with 11.4%, 8.6%, and 2.9%, respectively, in the control group (P<0.001). Between-group differences were seen for many intraoral QST: mechanical detection threshold, mechanical pain threshold (pinprick), dynamic mechanical allodynia (brush), dynamic mechanical allodynia (vibration), wind-up ratio, and pressure pain threshold (P<0.01). In the trigeminal area, between-group differences in thermal thresholds were nonsignificant while differences in cold detection at the thenar eminence were significant. Individual somatosensory profiles revealed complex patterns with hyper- and hyposensitivity to intraoral QST. Between-group differences in pressure pain thresholds (P<0.02) were observed at the thenar eminence. In conclusion, significant abnormalities in intraoral somatosensory function were observed in AO, which may reflect peripheral and central sensitization of trigeminal pathways. More generalized sensitization of the nociceptive system may also be part of AO pathophysiology.     

Functional Characterization of At-Level Hypersensitivity in Patients With Spinal Cord Injury

At-level and above-level hypersensitivity was assessed in patients with chronic complete thoracic spinal cord injury (SCI). Patients were classified using somatosensory mapping (brush, cold, pinprick) and assigned into 2 groups (ie, patients with at-level hypersensitivity [SCIHs, n = 8] and without at-level hypersensitivity [SCINHs, n = 7]). Gender and age-matched healthy subjects served as controls. Quantitative sensory testing (QST), electrically- and histamine-induced pain and itch, laser Doppler imaging, and laser-evoked potentials (LEP) were recorded at-level and above-level in SCI-patients. Six of 8 SCIHs, but 0 of 7 SCINHs patients suffered from neuropathic below-level pain. Clinical sensory mapping revealed spreading of hypersensitivity to more cranial areas (above-level) in 3 SCIHs. Cold pain threshold measures confirmed clinical hypersensitivity at-level in SCIHs. At-level and above-level hypersensitivity to electrical stimulation did not differ significantly between SCIHs and SCINHs. Mechanical allodynia, cold, and pin-prick hypersensitivity did not relate to impaired sensory function (QST), axon reflex flare, or LEPs. Clinically assessed at-level hypersensitivity was linked to below-level neuropathic pain, suggesting neuronal hyperexcitability contributes to the development of neuropathic pain. However, electrically evoked pain was not significantly different between SCI patients. Thus, SCI-induced enhanced excitability of nociceptive processing does not necessarily lead to neuropathic pain. QST and LEP revealed no crucial role of deafferentation for hypersensitivity development after SCI.

Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex

In 14 patients with unilateral persistent idiopathic facial pain (PIFP), classified according to the criteria of the International Headache Society, and 16 age-matched control subjects sensory functions were examined on the face by quantitative sensory testing (QST). Additionally, the somatotopy of the primary somatosensory cortex (SI) to tactile input from the pain area was evaluated by means of magnetoencephalography. Previously reported abnormalities in PIFP as a dishabituation of the R2 component of the blink reflex and psychiatric disturbances were co-evaluated. Psychiatric evaluation included a Structured Clinical Interview for axis-I DSM IV disorders (SCID-I) and employment of the SCL-90-R and a depression scale (ADS). Thresholds to touch, pin prick, warm, cold, heat and pressure pain as well as the pain ratings to single and repetitive (perceptual wind up) painful pin prick stimuli did not indicate a significant sensory deficit or hyperactivity in the pain area when compared with the asymptomatic side nor when compared with the values of healthy control subjects. QST results were not significantly altered in patients (n=4) that showed an abnormal dishabituation of the R2 component of the blink reflex. The interhemispheric difference in distance between the cortical representation of the lip and the index finger did not differ between patients and control subjects. Psychiatric evaluation did not disclose significant abnormalities at a group level. It is concluded that PIFP is maintained by mechanisms which do not involve somatosensory processing of stimuli from the pain area.     

Reliability of thermal quantitative sensory testing: a systematic review

The use of quantitative sensory testing (QST) has become more widespread, with increasing focus on describing somatosensory profiles and pain mechanisms. However, the reliability of thermal QST has yet to be established. We systematically searched the literature using key medical databases. Independent reviewers evaluated reliability data using the Quality Appraisal for Reliability Studies checklist. Of the 21 studies we included in this review, we deemed 5 to have high methodological quality. Narrative analysis revealed that estimates of reliability varied considerably, but overall, the reliability of cold and warm detection thresholds ranged from poor to excellent, while heat and cold pain thresholds ranged from fair to excellent. The methodological quality of research investigating the reliability of thermal QST warrants improvement, particularly in terms of appropriate blinding. The results from this review showed considerable variability in the reliability of each thermal QST parameter.     

Classifying post‐stroke shoulder pain: Can the DN4 be helpful?

The etiology of post‐stroke shoulder pain (PSSP) is largely unclear and may involve both nociceptive and neuropathic mechanisms. No gold standard is present for PSSP diagnosis. The neuropathic pain diagnostic questionnaire (DN4), was originally developed to identify neuropathic pain in the clinical context. In this study we used the DN4 to categorize PSSP patients and compared symptoms and signs suggestive of either nociceptive or neuropathic pain. Pain complaints and sensory functions were compared between patients with chronic PSSP scoring at least four (DN4+, n=9) or less than four (DN4⁻, n=10) on the DN4. Pain was assessed using a numeric rating scale and the McGill pain questionnaire. Sensory functions were assessed using clinical examination and quantitative sensory testing combined with a cold pressor test. Patients classified as DN4+ reported constant pain, higher pain intensity, a higher impact of pain on daily living, more frequent loss of cold sensation, reduced QST thresholds at the unaffected side and increased QST thresholds at the affected side. Notably, several symptoms and signs suggestive of either neuropathic or nociceptive pain corresponded to the subgroups DN4+ and DN4⁻ respectively. However, since the pathophysiological mechanisms remain unclear and none of the sensory signs could be exclusively related to either DN4+ or DN4⁻, PSSP prognosis and treatment should not be solely based on the DN4. Nonetheless, a thorough assessment of neuropathic and nociceptive pain complaints and somatosensory functions should be included in the diagnostic work‐up of PSSP.     

Painful traumatic peripheral partial nerve injury‐sensory dysfunction profiles comparing outcomes of bedside examination and quantitative sensory testing

The primary aim of this retrospective study was to focusing on the relationship between individual outcomes of bedside examination (BE) and quantitative testing of somatosensory functions (QST) in 32 patients with painful traumatic partial nerve injury. In addition, the potential presence of common sensory dysfunction denominators has been probed. Patients with a history of traumatic partial nerve injury and ongoing pain were included if pain was confined to the entire or part of the innervation territory of the severed nerve and a bedside titration of the neuronanatomical borders confirmed sensory aberrations. An in‐depth BE and QST was then performed in the most painful area. Categorization of normal and pathological outcome for both BE and QST was based on time honoured clinical decision‐making using the healthy contralateral corresponding area as control. In patients with normal outcome or quantitative aberrations (i.e. hypo‐ or hyperesthesia) at BE and QST, the same individual outcome of touch sensation was reported by 48% of the patients, for cold in 54% and for warmth in 58%. The most common dysfunction found at both BE and QST was hypoesthesia, however with no common denominators in somatosensory dysfunction. In conclusion, this study demonstrated that not infrequently the individual outcome of BE and the corresponding QST measure differed, most frequently for touch sensibility. This finding is of outmost importance when QST outcomes are used to corroborate results from BE in the diagnostic situation.     

Test-Retest and Inter-Examiner Reliability of a Novel Bedside Quantitative Sensory Testing Battery in Postherpetic Neuralgia Patients

In health and disease, the somatosensory system has been interrogated with standardized research techniques, collectively referred to as quantitative sensory testing (QST). In neuropathic pain, QST has been used to characterize multiple sensory derangements. However, the use of QST outside the lab has been limited by several factors, including a lack of standardization, variability in procedural technique, and duration of testing that would be unacceptable for clinic. To address these shortcomings, the Neuropathic Pain Research Consortium designed an easy and low-cost “bedside” QST procedure. To test the hypothesis that this procedure would be clinically reliable over time and across different examiners, a multisite, blinded study was performed in subjects with postherpetic neuralgia. Generally, agreement between 2 examiners and over 2 study visits with 1 examiner was high. Additionally, intraclass correlation coefficients and Kappa statistics calculated showed that the battery of QST tests included were highly reliable. Interestingly, mechanical modalities (light brush, pinprick, pressure, and vibration) showed the highest reliability. The least reliable modalities were cool (room temperature) and warmth (38°C). These data demonstrate that the Neuropathic Pain Research Consortium beside QST protocol is reliable across examiner and over time, providing a validated QST tool for use in clinical practice and clinical trials.PerspectiveThis blinded, multicenter trial in 32 patients with postherpetic neuralgia demonstrates bedside QST is reliable and suitable as a clinical trial outcome. The novel bedside battery could be used in clinical trials or in clinical practice over time given the reliability data presented in this article.     

Modulation of Somatosensory Profiles by Spinal Cord Stimulation in Primary Raynaud′s Syndrome

Background and Goal: Spinal cord stimulation (SCS) is an effective antinociceptive treatment for various neuropathic pain syndromes. Apart from antinociceptive action, it may modulate overall somatosensory perception. This case report targets the question of whether SCS may alter quantitative sensory testing (QST) in a patient with primary Raynaud′s syndrome. Materials and Methods: We report on a 44‐year‐old female patient with primary Raynaud′s syndrome who had SCS via cervical and lumbar electrodes. QST was performed in a standardized manner assessing cold detection threshold (CDT) and warm detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) thresholds, and vibration detection threshold (VDT) and pressure pain thresholds (PPT). We tested at the dorsum of the right/left hand of the patient with engaged and disengaged SCS. Test results were compared with a control group of 80 subjects. Results: Without SCS, the patient showed a sensory decrease in CDT, MDT, MPT, and VDT. SCS influenced the perception of cold, warm, and tactile detection thresholds, whereby CDT, WDT, and VDT were impaired and MDT was improved. Conclusion: SCS significantly modulated the somatosensory profile in a patient with primary Raynaud′s syndrome. These effects were pronounced in qualities involving Aβ, C, and A? nerve fibers. Further investigations may help to understand the mechanisms of action of SCS.     

Sex Differences in Interleukin-6 Responses Over Time Following Laboratory Pain Testing Among Patients With Knee Osteoarthritis

Epidemiological studies suggest that women are not only at a higher risk for developing knee osteoarthritis (KOA), but also report greater symptom severity compared to men. One potential underlying mechanism of these sex differences may be exaggerated inflammatory responses to pain among women compared to men. The present study examined sex differences in interleukin-6 (IL-6) response over time following experimental pain testing. We hypothesized that women, when compared to men, would show greater IL-6 reactivity when exposed to acute pain in a human laboratory setting. Eighty-four participants (36 men and 48 women) with KOA scheduled for total knee arthroplasty underwent a quantitative sensory testing (QST) battery. A total of seven IL-6 measurements were taken, twice at baseline, once immediately after QST, and every 30 minutes up to 2 hours after QST. Consistent with our hypothesis, women, when compared to men, showed accelerated increases in IL-6 levels following laboratory-evoked pain, even after controlling for body mass index, marital status, clinical pain, evoked pain sensitivity, and situational pain catastrophizing. Given that KOA is a chronic condition, and individuals with KOA frequently experience pain, these sex differences in IL-6 reactivity may contribute to the maintenance and/or exacerbation of KOA symptoms.PerspectivesThe present study demonstrates that women, when compared to men, exhibit greater IL-6 reactivity after exposure to laboratory-evoked pain. Such sex differences may explain the mechanisms underlying women's higher chronic pain risk and pain perception, as well as provide further insight in developing personalized pain interventions.     

The influence of pain intensity on somatosensory perception in patients suffering from subacute/chronic lateral epicondylalgia.

A confounding factor in the analysis of chronic pain patients is the finding of signs of somatosensory disturbances not only in neuropathic pain patients but also in a subgroup of patients with musculoskeletal pain. The purpose was to investigate if patients suffering from subacute/chronic lateral epicondylalgia demonstrated altered sensibility, and if this was affected by pain intensity. At the start of the experiment, quantitative sensory testing (QST) (thermal, pressure pain, touch) was performed in the local pain area and in the area of pain referral. QST was repeated following pain provocation (weight lifting). A local anaesthetic was then injected into the lateral epicondyle and QST was repeated in the area of pain referral. The contralateral arm was assessed, treated and injected in the same way. At the baseline assessment there was no difference in sensibility between sides, with the exception of a significantly lowered threshold to noxious heat (p<0.04) in the area of pain referral, present during the whole experiment. In the affected arm only, weight lifting resulted in significantly increased pain intensity in the local (p<0.01) and referred (p<0.01) pain areas, respectively. Repeated muscle contractions resulted in altered somatosensory functions in both the affected arm and the unaffected arm, consequently not dependent on ongoing pain in the assessed area. Tactile perception thresholds increased significantly following pain provocation in the area of pain referral (p<0.04) only and normalized following injection of local anaesthetic (p<0.02), indicating that the sensitivity to light touch was altered by the nociceptive input from the affected arm.     

Pharmacologic treatment of complex regional pain syndrome I: a conceptual framework

Pain may be a leading symptom in complex regional pain syndrome type I (CRPS I) and may hinder functional recovery. In this case, a pharmacotherapeutic approach to pain should be part of the individually tailored interdisciplinary treatment regimen. However, operational criteria for determining which patient may profit from what therapeutic intervention are lacking. This article discusses a conceptual framework in which the rapid progress made in basic pain research may contribute to the clinical management of pain in CRPS I. First, recent insights in the pathophysiologic mechanisms underlying CRPS I are reviewed. CRPS I is considered a neuropathic pain syndrome with a mixed and time-dependent profile of a regional inflammation, sensitization of primary somatosensory afferents (peripheral sensitization), and sensitization of spinal neurons (central sensitization). The dominant mechanisms may vary across individual patients with different time profiles. Second, a model was constructed in which signs and symptoms in an individual patient are related to these mechanisms. Finally, relating the clinical picture to the underlying pathophysiology may help determine the pharmacotherapeutic approach for an individual patient. Pharmacologic options are discussed in this context. The presented framework does not aim to provide an evidence-based treatment algorithm, ready to be used in daily clinical practice; rather it offers a crude, first step toward a mechanism-based pharmacotherapy in CRPS I, in an effort to shift from a mainly empirical treatment paradigm toward theory-driven treatment procedures.     

Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent?

Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra‐median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty‐six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms.