A pain model with a neuropathic somatosensory lesion: Morton neuroma

A randomized, double-blind, three-period cross-over study was performed to characterize the sensory phenotype and pain demographics in patients with Morton neuroma (n = 27) and to explore the effects of local administration (2 mL) of placebo and lidocaine (1 and 10 mg/mL) around the neuroma. Using the pain quality assessment scale (PQAS), the highest rating was seen for unpleasant pain and intensity of deep pain and the lowest for sensitive skin. Ongoing pain was reported in 32% of patients. Patients reported mild to moderate average pain, and that pain had interfered with sleep only marginally. Quantitative sensory testing (QST) measurements in the innervation territory showed hypophenomena or hyperphenomena in all patients, indicating that all had neuropathy. There was no particular QST modality that appeared to be specifically affected. Even the high-dose lidocaine resulted in limited effects on nerve-impulse conduction as judged by the effect on QST variables. However, both doses of lidocaine significantly reduced pain after step-ups, compared to placebo, indicating that lidocaine in this setting affected predominantly impulse generation and not impulse conduction. Following placebo treatment, pain after step-ups was similar in patients with and without hyperalgesia, indicating that the presence of hyperalgesia does not affect the pain intensity evoked by step-ups or walking.     

Évaluation quantitative des troubles sensitifs et des douleurs neuropathiques

Quantitative sensory testing (QST) may be defined as the analysis of perception of pain in response to thermal and mechanical stimuli of measured intensity. This method uses thermal, mechanical and vibratory stimuli, enabling the measurement of pain thresholds and sensations caused by suprathreshold stimulation. QST can quantify hypoesthesia (raised detection thresholds), allodynia (lowered pain thresholds) and hyperalgesia (increased response to suprathreshold stimuli). It is suitable for detecting or monitoring peripheral polyneuropathies characterized by fine fiber impairment, particularly diabetic peripheral neuropathies. It has also been used to analyse the pathophysiological mechanisms involved in certain neuropathic pain conditions and to assess the effects of treatments for neuropathic pain. In this paper the relevance and limitations of QST for the assessment of neuropathic pain and its treatment are discussed.     

Quantitative Sensory Testing of Neuropathic Pain Patients: Potential Mechanistic and Therapeutic Implications

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.     

Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements

Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p < 0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.     

Zusammenhang von Quantitativer Sensorischer Testung und Fragebögen zu neuropathischen Schmerzen am Beispiel chronischer Ischämieschmerzen bei PAVK

Background

A neuropathic component to chronic ischemic pain in peripheral arterial disease (PAD) has recently been shown using quantitative sensory testing (QST) and pain questionnaires. The aim of this study was to examine correlations between QST and pain questionnaires in patients with chronic ischemic pain.

Methods

A total of 10 patients with severe PAD (Fontaine stages III and IV) without diabetes mellitus answered a questionnaire and were examined with QST. The questionnaire consisted of several validated instruments which were used to examine the intensity of pain, quality of pain and neuropathic pain (VAS, SF-MPQ, S-LANSS, NPSI).

Results

The results of the QST confirmed previously published data. Several terms of the SF-MPQ showed a correlation with parameters of the QST, such as Allodynia (QST) which correlated with the term tender (SF-MPQ) (Spearman’s correlation coefficient 0.911; p≤0.001) and the NPSI subscore evoked pain correlated with the QST parameter wind-up ratio (0.683; p=0.042).

Conclusion

The results suggest that there might be correlations between psychophysical tests (QST) and pain questionnaires. Subjective perceptions of pain might be represented by a certain pattern in the QST. These connections could contribute to further clarify the pathophysiologic mechanisms leading to the perception of pain.     

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.

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.     

Neurophysiologic and quantitative sensory testing in the diagnosis of trigeminal neuropathy and neuropathic pain

This study investigated the utility of neurophysiologic examination and thermal quantitative sensory testing (QST) in the diagnosis of trigeminal neuropathy and neuropathic pain. Fifty-eight patients (14 men), 34 with sensory deficit within the inferior alveolar nerve (IAN) and 24 within the lingual nerve (LN) distribution, were included. Twenty-six patients (45%) reported neuropathic pain. Patients underwent blink reflex (BR) test and thermal QST; sensory neurography was done to the IAN patients. Results of clinical sensory testing were available from the charts of 48 patients revealing abnormal findings in 77% of the IAN and in 94% of the LN patients. The BR test was abnormal in 41%, neurography in 96%, and QST in 91% of the IAN patients. In the LN group, BR was abnormal in 33%, and QST in 100% of the patients tested. Neurophysiologic tests and QST verified the subjective sensory alteration in all but 2 IAN patients, both with old injuries, and 4 LN patients who did not undergo QST. When abnormal, thermal QST showed elevation of warm and cold detection thresholds (hypo/anesthesia), hypoalgesia was less marked, and heat allodynia was only occasionally present. Contralateral thermal hypoesthesia after unilateral injury was found in 14 patients. It was associated with the occurrence of neuropathic pain (P=0.016). Axonal Abeta afferent damage was less severe in the IAN patients with pain than in those without pain (P=0.012). Neurophysiologic tests and thermal QST provide sensitive tools for accurate diagnosis of trigeminal neuropathy and study of pathophysiological features characteristic to human neuropathic pain.     

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.     

Quantitative assessment of neuropathic pain

Quantitative sensory testing (QST) refers to a group of protocols that allows for quantitative measures of somesthetic function. Several protocols evaluate perceptual threshold, whereas others evaluate perception of stimuli above threshold. Each protocol has its own advantages and disadvantages, but one must always weigh a trade-off between accuracy (with longer protocols) and expediency (with shorter protocols). In assessing patients with neuropathic pain, one is interested in both positive and negative sensory symptoms. QST studies, using either neuropathic pain patients or healthy volunteers who have been rendered temporarily hyperalgesic, have demonstrated that pain abnormalities can be modality specific. The fact that various pain abnormalities can exist independently of each other suggests that (at least partially) different neuropathologic processes are responsible for each one. Current research suggests that both peripheral sensitization and central sensitization play a role in these abnormal pain conditions, and identification of precise neuropathologic mechanisms is under active investigation.     

Can pain can be more or less neuropathic? Comparison of symptom assessment tools with ratings of certainty by clinicians

Chronic pain is generally regarded as being divided into two mutually exclusive pain mechanisms: nociceptive and neuropathic. Recently, this dichotomous approach has been questioned and a model of chronic pain being 'more or less neuropathic' has been suggested. To test whether such a spectrum exists, we examined responses by patients with chronic pain to validated neuropathic pain assessment tools and compared these with ratings of certainty about the neuropathic origin of pain by their specialist pain physicians. We examined 200 patients (100 each with nociceptive and neuropathic pain) and administered the self-complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS score) and the Neuropathic Pain Scale (NPS). Clinicians were asked to rate their certainty of the presence of neuropathic pain mechanisms on a 100 mm visual analogue scale (VAS) (0='not at all neuropathic in origin' to 100='completely neuropathic in origin'). The whole sample was divided into tertiles based on ascending ratings of diagnostic certainty by clinicians using the VAS and labelled 'unlikely', 'possible' and 'definite' neuropathic pain. There were significant differences in median S-LANSS and NPS composite scores between all tertile groups. There were also significant differences between many S-LANSS and NPS item scores between groups. We have shown that higher scores on both the S-LANSS and the NPS are indicative of greater clinician certainty of neuropathic pain mechanisms being present. These data support the theoretical construct that pain can be more or less neuropathic and that pain of predominantly neuropathic origin may be a useful clinical concept.     

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.     

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.     

Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. (Department of Pain Medicine and Palliative Care, Beth Lsrael Medical Center, New York, NY) Clin J Pain 2000;16:205–208.

Our goal was to perform a pilot, open‐label, prospective study to access the effectiveness and tolerability of a topical lidocaine patch (Lidoderm) for the treatment of peripheral neuropathic pain conditions other than postherpetic neuralgia. Sixteen patients with refractory peripheral neruopathic pain conditions who had reported intolerable side effects or inadequate pain relief with antidepressant, anticonvulsant, antiarrhythmic, and opioid medications participated in this study. Diagnoses included postthoracotomy pain, stump neuroma pain, intercostal neuralgia, diabetic polyneuropathy, meralgia paresthetica, complex regional pain syndrome, radiculopathy, and postmastectomy pain. A 6‐item Pain Relief Scale was used. Moderate or better pain relief was reported by 13 of the 16 participants (81%). One patient stopped treatment after 4 days due to lack of relief. The remaining 15 patients had a mean duration of patch use of 6.2 weeks with continued relief. Only 1 patient reported a side effect, a mild skin irritation. Conclude the Lidoderm patch provides clinically meaningful pain relief in most of these refractory neuropathic pain patients without side effects. Controlled trials need to be performed to confirm these preliminary findings. Comment by Tat‐Leang Lee, M.D. This is an interesting study that highlighted a simple, efficacious method for the treatment of resistant neuropathic pain. As this was a pilot study using an open‐label method, and treating a heterogenous group of neuropathic pain conditions, caution should be adopted in the interpretation of the results. What remains unanswered is the reason for the success of the lidocaine patch, particularly when previous studies have documented the failure of EMLA in the treatment of neuropathic pain. Indeed, several patients who participated in this study had used EMLA unsuccessfully before, although no details on its administration was reported. Both the lidocaine patch and EMLA contain 5% lidocaine, which presumably would result in greater penetration by the EMLA cream. Therefore, a placebo‐controlled randomized trial is needed to confirm the findings of this pilot study. Nevertheless, this is a promising treatment that is convenient, lacks systemic effect, easily added‐on to existing treatment, and with only minor side effects, that is worth considering for our patients.     

Neurology (57)

New analgesics for neuropathic pain: the lidocaine patch. (North Shore University Hospital, Syosset, NY) Clin J Pain 2000;16:S62–266.
This article reviewed the basis for the development of the lidocaine patch and reviewed the reports of the clinical studies published. Potential uses of the lidocaine patch for other conditions in addition to postherpetic neuralgia (PHN) were also discussed. Conclude that it has been clearly established that the lidocaine patch is a safe and effective treatment for PHN and it is recommended as a first-line treatment based on demonstrated efficacy, quick onset of action, lack of systemic effects, and ease of use with other treatments.
Comment by Enrique Reig, MD.
Intravenous lidocaine is used in pain units for the transient relief of chronic neuropathic pain. If the analgesic result is satisfactory, some physicians start treatment with a lidocaine analogue, oral mexylithene. However, the latter drug is not always well tolerated and its efficacy (in my opinion) is far lower than that of intravenous lidocaine. The recently marketed lidocaine patch is a highly recommended therapeutic alternative if we are considering long-term treatment with lidocaine. Topical agents act locally (skin, soft tissues, peripheral nerves) and do not cause high blood levels (no higher than 0.6 micgr/mL). Topical 5% lidocaine decreases the ectopic discharges from peripheral afferents, reducing nociceptive input to the CNS. There are few side effects and the main indication is postherpetic neuralgia and all those syndromes with peripheral neuropathic pain. The relief that can be expected after using topical 5% lidocaine is not complete, and it can be associated with other types of drugs (anticonvulsants, antidepressants, analgesics, etc.) to obtain a synergistic effect.     

Test order of quantitative sensory testing facilitates mechanical hyperalgesia in healthy volunteers

Quantitative sensory testing (QST) has become a widely used method to evaluate different submodalities of the somatic sensory system (predominantly) in patients with neuropathic pain. QST consists of 7 tests measuring 13 parameters in order to assess and quantify the perception of temperature, touch, pain, pressure, and vibration. The German Research Network on Neuropathic Pain implemented a standardized QST protocol including a defined testing order of the measurements. Accordingly, subjects tested with QST undergo thermal before mechanical testing. In the present study, we investigated the effect of testing order on the results of QST. Twenty healthy subjects were tested twice, 1 week apart with 2 different QST testing orders: the standardized testing order according to the German Research Network on Neuropathic Pain and a modified testing order in which mechanical stimuli were applied before thermal stimuli. For the test protocol that began with thermal testing, subjects exhibited signs of an increased mechanical perception: The mechanical pain sensitivity was significantly increased (P = .001, Wilcoxon test) for each pinprick stimulator and the mechanical pain threshold was lowered by a factor of 2 when compared with the modified testing order in which mechanical parameters were tested at the beginning of the session without prior thermal stimulation. Thermal parameters were the same for both test-order paradigms. These data indicate that preceding mild thermal stimulation might lead to a sensitization to mechanical stimuli and thus to mechanical hyperalgesia. Alternative habituation mechanisms in the modified testing order resulting from repeated pinprick stimulation at the beginning should also be debated. QST is a helpful diagnostic tool but interpretation should be done with consideration of interaction between test parameters. Reference data are only valid in the testing order from which they are obtained. PERSPECTIVE: Present data showed that mechanical hyperalgesia followed thermal testing. This article demonstrates that the test order of quantitative sensory testing is relevant in interpreting the results obtained. Reference values are suitable in the test order from which they are obtained.     

PEER systematic review of randomized controlled trials: Management of chronic neuropathic pain in primary care

ObjectiveTo determine the proportion of patients with neuropathic pain who achieve a clinically meaningful improvement in their pain with the use of different pharmacologic and nonpharmacologic treatments.Data sourcesMEDLINE, EMBASE, the Cochrane Library, and a gray literature search.Study selectionRandomized controlled trials that reported a responder analysis of adults with neuropathic pain—specifically diabetic neuropathy, postherpetic neuralgia, or trigeminal neuralgia—treated with any of the following 8 treatments: exercise, acupuncture, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), topical rubefacients, opioids, anticonvulsant medications, and topical lidocaine.SynthesisA total of 67 randomized controlled trials were included. There was moderate certainty of evidence that anticonvulsant medications (risk ratio of 1.54; 95% CI 1.45 to 1.63; number needed to treat [NNT] of 7) and SNRIs (risk ratio of 1.45; 95% CI 1.33 to 1.59; NNT = 7) might provide a clinically meaningful benefit to patients with neuropathic pain. There was low certainty of evidence for a clinically meaningful benefit for rubefacients (ie, capsaicin; NNT = 7) and opioids (NNT = 8), and very low certainty of evidence for TCAs. Very low-quality evidence demonstrated that acupuncture was ineffective. All drug classes, except TCAs, had a greater likelihood of deriving a clinically meaningful benefit than having withdrawals due to adverse events (number needed to harm between 12 and 15). No trials met the inclusion criteria for exercise or lidocaine, nor were any trials identified for trigeminal neuralgia.ConclusionThere is moderate certainty of evidence that anticonvulsant medications and SNRIs provide a clinically meaningful reduction in pain in those with neuropathic pain, with lower certainty of evidence for rubefacients and opioids, and very low certainty of evidence for TCAs. Owing to low-quality evidence for many interventions, future high-quality trials that report responder analyses will be important to strengthen understanding of the relative benefits and harms of treatments in patients with neuropathic pain.     

Role of Small-Fiber Afferents in Pain Mechanisms With Implications on Diagnosis and Treatment

Numerous mechanisms are implicated in the perception of pain. Although many anatomical, molecular, and functional components have been identified, a comprehensive and integrated theory of pain perception has yet to be firmly established that fits the diverse clinical experience. Acute pain involves the activation of several varieties of small primary sensory neurons, collectively termed nociceptors, which have small-caliber unmyelinated or myelinated axons (C and Aδ fibers, respectively) that innervate all body tissues. They are stimulated by noxious stimuli that activate ion channels on the endings either directly or through the release of cytokines from damaged or stressed tissues. A variety of drugs successfully treats acute pain by targeting these ion channels or cytokine interactions. Paradoxically, several chronic neuropathic pain conditions are associated with a loss of small-caliber axons and have an unpredictable and poor response to current drugs, especially at doses that do not cause severe side effects. In an attempt to further an integrated theory of pain perception, this review focuses upon the presumed role of small-caliber innervation, particularly to the epidermis and cutaneous vasculature, and the clinical manifestations, diagnosis, and treatment of pathologies of this innervation.     

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.