Maike Stengel

Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study.

&NA; Quantitative sensory testing (QST) is an instrument to assess positive and negative sensory signs, helping to identify mechanisms underlying pathologic pain conditions. In this study, we evaluated the test–retest reliability (TR‐R) and the interobserver reliability (IO‐R) of QST in patients with sensory disturbances of different etiologies. In 4 centres, 60 patients (37 male and 23 female, 56.4 ± 1.9 years) with lesions or diseases of the somatosensory system were included. QST comprised 13 parameters including detection and pain thresholds for thermal and mechanical stimuli. QST was performed in the clinically most affected test area and a less or unaffected control area in a morning and an afternoon session on 2 consecutive days by examiner pairs (4 QSTs/patient). For both, TR‐R and IO‐R, there were high correlations (r = 0.80–0.93) at the affected test area, except for wind‐up ratio (TR‐R: r = 0.67; IO‐R: r = 0.56) and paradoxical heat sensations (TR‐R: r = 0.35; IO‐R: r = 0.44). Mean IO‐R (r = 0.83, 31% unexplained variance) was slightly lower than TR‐R (r = 0.86, 26% unexplained variance, P < .05); the difference in variance amounted to 5%. There were no differences between study centres. In a subgroup with an unaffected control area (n = 43), reliabilities were significantly better in the test area (TR‐R: r = 0.86; IO‐R: r = 0.83) than in the control area (TR‐R: r = 0.79; IO‐R: r = 0.71, each P < .01), suggesting that disease‐related systematic variance enhances reliability of QST. We conclude that standardized QST performed by trained examiners is a valuable diagnostic instrument with good test–retest and interobserver reliability within 2 days. With standardized training, observer bias is much lower than random variance. Quantitative sensory testing performed by trained examiners is a valuable diagnostic instrument with good interobserver and test–retest reliability for use in patients with sensory disturbances of different etiologies to help identify mechanisms of neuropathic and non‐neuropathic pain.

Topical High-Concentration (40%) Menthol-Somatosensory Profile of a Human Surrogate Pain Model

UNLABELLED Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain. Topical application of menthol has been proposed as model to study cold hyperalgesia. The aim of this psychophysical study was to characterize the human surrogate of neuropathic pain of topical menthol application by using a standardized and validated protocol of quantitative sensory testing (QST). Additionally, we assessed the course of the signs elicited by menthol application over time. High-concentration 40% L-menthol was applied topically on hairy skin in 12 healthy subjects. Standardized psychophysical tests (QST) assessing 13 parameters including thermal and mechanical detection and pain thresholds were obtained before and every 45 minutes after menthol removal up to 4 hours after menthol application. Menthol decreased the cold pain threshold, mechanical pain threshold, and increased the mechanical pain sensitivity in all subjects displaying cold and mechanical pinprick hyperalgesia. In all subjects, an area of secondary pinprick hyperalgesia could be determined. Within the observation time, the decreased cold pain threshold increased continuously, whereas the signs of primary and secondary pinprick hyperalgesia remained stable. The data suggest that topical 40% menthol application is a useful model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. PERSPECTIVE This study establishes the topical application of high-concentration 40% menthol as a useful stable model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. The provided long-term data are important for psychophysical and pharmacological research in humans and provide us with insights on experimental cold and mechanical hyperalgesia.

A case of neuropathic brachioradial pruritus caused by cervical disc herniation.

Background A 64-year-old woman presented to an outpatient clinic with a 2-year history of itch, burning sensation and intermittent paresthesias within the innervation territory of the sixth cervical nerve root on the right dorsal forearm. No dermatological diseases, trauma to the affected extremity or the spine, or familial pruritus were reported.Investigations Dermatological examination, skin biopsy, laser Doppler imaging, neurological physical examination and cervical MRI scan.Diagnosis Brachioradial pruritus caused by cervical disc herniation.Management Ventral spinal fusion with cage implantation.

Oxaliplatin-induced painful neuropathy--flicker of hope or hopeless pain?

Oxaliplatin is a third-generation organoplatinum compound with significant activity against colorectal cancer. Unlike other platinum compounds oxaliplatin induces an acute form of painful neuropathy which appears soon after administration and is often transient and reversible within days. The patients suffer from extremity and perioral paresthesias and in particular from severe cold hypersensitivity. After multiple cycles 70% of the patients develop a clinically different peripheral neuropathy that is characterized by a sensory axonal nerve damage closely resembling that induced by cisplatin. This chronic neuropathy can become very disabling and is, in fact often a limiting factor for escalating chemotherapeutic dose. For this reason, it would be very valuable to predict oxaliplatin neurotoxicity early in the course of treatment. In this issue of Pain, Attal and colleagues [1] very elegantly unravelled clinical markers manifesting during the first oxaliplatin treatment cycles, which are associated with the development of chronic toxic polyneuropathy. They used quantitative sensory testing (QST) to study in detail the somatosensory signs of acute oxaliplatin neuropathy, administered questionnaires to assess these symptoms and correlated the results with the risk of developing chronic neuropathy after 12 months. In particular, cold allodynia and hyperalgesia of the hands, measured two weeks after the third chemotherapeutic cycle, predicted severe chronic neuropathy as evaluated with the neurosensory scale of the national cancer institute NCI-CTC. The severity of neuropathy also correlated with the duration of cold-evoked symptoms, intensity of neuropathic symptoms and intensity of cold-evoked pain. Early identification of vulnerable patients who are at high risk of developing a severe chronic neuropathy is important for patient management as well as for future research approaches:

462 TOPICAL MENTHOL: STABILITY OF A SENSORY PROFILE IN A HUMAN SURROGATE MODEL

We compared the morphology, latency, amplitude, scalp topography and intracranial generators of laser evoked potentials (LEPs) obtained in response to a CO2 (wavelength 10.6 lm) and a Nd:YAP (wavelength 1.34 lm) laser stimulators. 32-channel LEPs and reaction times were recorded in 11 healthy subjects (6 males and 5 females, mean age 39 ± 10 years). Laser stimuli were delivered on the dorsum of the right and left hands (intensity slightly above pain threshold, matched for each individual). For both the CO2 and YAP lasers stimulations we obtained classical N1/P1, N2 and P2 LEP components with similar topographic distribution. As compared with the responses obtained by the CO2, responses evoked by the Nd:YAP had significantly earlier latencies (30 ms) and were more synchronised, yielding higher N2 amplitudes that those obtained with a CO2 laser ( 14 lV vs. 6 lV). For both YAP and CO2 lasers, source localization analyses showed a similar distribution of intracranial generators. The early N1/P1 component was dominated by an insular activity more pronounced for the YAP laser. The late N2–P2 component was dominated by a singular activity. In conclusion, both CO2 and YAP lasers stimulations induced similar and very reproducible LEPs, obeying to the same generators. However, the fact that YAP responses are quicker and its N2 larger in amplitude suggests a more efficient recruitment of nociceptive fibers by this type of laser beam. This study permitted to collect normative data of LEPs obtained by both CO2 and YAP lasers, which should be useful in clinical and/or experimental research.

Pathophysiologie neuropathischer Schmerzen

ZusammenfassungNeuropathische Schmerzen sind Syndrome, die aufgrund einer Schädigung des nozizeptiven Systems entstehen; sowohl Läsionen an peripheren Neuronen als auch an zentralnervösen Strukturen können eine neuropathische Schmerzsymptomatik auslösen. Die zugrunde liegenden Schädigungsmechanismen sind vielfältig: mechanische, metabolische, toxische oder entzündliche Traumen verursachen eine biochemische, morphologische und physiologische Veränderung der betroffenen Neuronen. Pathophysiologische Vorgänge wie die periphere und zentrale Sensibilisierung sowie die folgende Degeneration des inhibitorischen Systems führen im Weiteren häufig zu einer Schmerzchronifizierung. Diese Veränderungen können mit der Zeit irreversibel werden und trotz Gewebeheilung fortbestehen. Wichtig bei neuropathischen Schmerzen, die sich klinisch charakteristischerweise durch brennende Spontanschmerzen, einschießende Schmerzattacken und evozierte Schmerzen darstellen, ist somit neben einer kausalen Therapie auch eine symptomatische, medikamentöse Behandlung, die in die pathophysiologischen Prozesse eingreift.AbstractNeuropathic pain syndromes are generated by the impairment of nociceptive pathways. Both lesions of the peripheral and central nervous system may cause such pain. There are multifarious damage mechanisms: mechanical, metabolic, toxic or inflammatory injuries lead to biochemical, morphological and physiological changes of the affected neurons. Pathophysiological processes, such as peripheral and central sensitization, as well as degeneration of the inhibitory system, often result in neuropathic pain becoming chronic. These changes may become irreversible with time and persist in spite of the healing of the injured tissue. Neuropathic pain syndromes are clinically characterized by spontaneous pain (ongoing, paroxysms) and evoked types of pain (hyperalgesia, allodynia). An important aim in addition to causal treatment is symptomatic pain therapy, which inhibits the pathophysiological processes of pain.

472 ENDOTHELIAL DYSFUNCTION IN COLD TYPE CRPS

Later the intradural tumor (haemangiopericytoma) under C8 root right was diagnosed and removed. Patient No. 3 ([posterior] tibial nerve) and patient No. 4 (common peroneal nerve): Both patients had history of rectal carcinoma. They suffered with problems mimicking peripheral nerve entrapment neuropathy. The metastasis of carcinoma in the pelvis was established later. Conclusions: We have to keep on mind the malignant disease in a patient’s history and exclude malignant origin of his/her problems, especially when it can avoid unnecessary operations.

473 SKIN TEMPERATURE DIFFERENCES IN CRPS AND HEALTHY CONTROLS

Later the intradural tumor (haemangiopericytoma) under C8 root right was diagnosed and removed. Patient No. 3 ([posterior] tibial nerve) and patient No. 4 (common peroneal nerve): Both patients had history of rectal carcinoma. They suffered with problems mimicking peripheral nerve entrapment neuropathy. The metastasis of carcinoma in the pelvis was established later. Conclusions: We have to keep on mind the malignant disease in a patient’s history and exclude malignant origin of his/her problems, especially when it can avoid unnecessary operations.

461 SPECIFIC SENSORY PROFILE IN FABRY PATIENTS WITH NEUROPATHIC PAIN

Background and Aims: Patients with failed back surgery syndrome (FBSS) continue to experience persistent or recurrent pain, disability and reduced quality of life despite anatomically successful lumbosacral spine surgery. The aim of this randomised controlled trial was to evaluate the clinical (and cost-) effectiveness of the addition of spinal cord stimulation (SCS) to conventional medical management (CMM) of patients with FBSS. Methods: 100 patients suffering from persistent neuropathic pain predominantly in the legs were randomised to receive SCS utilising the SynergyTM neurostimulator (Medtronic Inc, Minneapolis) plus CMM or CMM alone. Patients in either group received appropriate adjuvant therapy (excluding spinal surgery or intrathecal drug delivery) and were followed up to 24months, with crossover after the 6-month visit upon patient request. Pain relief (>50% change on VAS), functional capacity (Oswestry), health related quality of life (HRQoL assessed by Short-Form 36), patient satisfaction and adverse effects were assessed at each study visit. Results: In an intention to treat analysis at 6-months, patients randomised to SCS experienced the following improvements when compared to CMM alone: significantly more leg pain relief (P = 0.0001), improved functionality (P = 0.0002), improved HRQoL in 7 out of 8 domains (0.02> P >0.0002) and greater satisfaction in their treatment (P< 0.0004). Fourteen (29%) of the 48 patients who received a stimulator had a complication that required additional surgery. Conclusions: Compared to CMM alone, SCS improves pain relief, healthrelated quality of life and functionality in predominantly neuropathic FBSS patients at 6 months. The 12-month follow up will be completed in July 2006.