[Complex regional pain syndrome (CRPS) : An update]. / Das komplexe regionale Schmerzsyndrom (CRPS) : Ein Update.

The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

[Complex regional pain syndrome (CRPS) : An update]. / Das komplexe regionale Schmerzsyndrom (CRPS) : Ein Update.

The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

[Pain - a neglected neurological issue]. / Schmerz - ein vernachlässigtes neurologisches Thema.

Chronic pain represents a great challenge; according to epidemiological data increasing numbers of patients should be expected. Based on recent advances, a better understanding of the pathophysiology of chronic pain has been achieved and neurologists have made a major contribution to this understanding. Chronic pain is accompanied by substantial maladaptive plastic alterations in both the peripheral and central nervous systems; therefore, neurological knowledge is of paramount importance for pain therapists but this contrasts with the current treatment situation of pain patients in Germany. There are basically too few departments and practices undertaking treatment, and neurologists are an exception in most pain centers. Furthermore, due to economic reasons neurological hospitals are currently experiencing a dearth of inpatients suffering from chronic pain. Diagnostic and/or treatment procedures for neurological pain entities (e.g. headaches or neuropathic pain) are insufficiently represented in the German diagnosis-related groups (DRG) reimbursement system and the obstacles for an efficient pain therapy in neurological practices are too high. Finally, there are too few academic positions for pain medicine in neurological hospitals; therefore, career opportunities for motivated young neurologists with an interest in pain are lacking. In order to address the unmet therapeutic needs of patients with chronic pain there is a high demand for (i) establishment of departments for neurological pain medicine, (ii) modification of the German DRG system and (iii) education of young neurologists with expertise in pain. Pain medicine in particular should be especially appealing to neurologists .

[Pain-relieving effect of CGRP antagonism on inflammatory pain]. / Lindernde Wirkung des CGRP-Antagonismus auf Entzündungsschmerz.

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain; however, its implication in inflammatory processes is not well known. The CGRP receptor antagonist BIBN4096BS was shown to reduce migraine pain and trigeminal neuronal activity. An analgesic action of this compound can also be found in rats with induced acute inflammation by injection of complete Freund's adjuvant (CFA) in one hindpaw. In this model the compound reduced inflammatory pain and spinal neuronal activity. Behavioral experiments (Randall-Selitto test) revealed a reversal of the CFA-induced mechanical hyperalgesia in rats after systemic drug administration. In vivo electrophysiological studies performed in rats injected with CFA using recordings of wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord, confirmed a reduction of neuronal activity after systemic drug administration. The same considerable amount of reduction occurred after topical administration onto the paw with resulting systemic plasma concentrations in the low nanomolar range. Spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model which suggests that peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.

[Current aspects of the therapy of complex regional pain syndrome]. / Aktuelles zur Therapie des komplex-regionalen Schmerzsyndroms.

BACKGROUND: Complex regional pain syndrome (CRPS) constitutes an enigmatic post-traumatic pain disorder. AIM OF THE STUDY: The paper provides state of the art knowledge about CRPS. RESULTS: The typical constellation of symptoms of CRPS includes pain, sensory disturbances, motor symptoms, disturbances of the autonomic control of the limbs and trophic changes. These symptoms generalize distally and go beyond single nerve innervation territories. Diagnosis is made based on clinical findings. Three-phase bone scintigraphy may be the best supporting technical investigation. Symptoms typically change during the course of CRPS. In the acute stage inflammatory symptoms prevail and during chronic stages the most expressed findings are related to central neuroplasticity. These findings include hyperalgesia, sensory loss, CRPS movement disorder, body perception disturbances and autonomic symptoms. Medical treatment with anti-inflammatory agents (steroids) or bisphosphonates is most effective in the early stages and DMSO cream might also be beneficial. Administration of i.v. ketamine has been proven effective against CRPS pain and physical therapy with behavioral components, such as pain exposure helps to overcome central reorganization and functional impairment. Psychotherapy should be offered if there are significant comorbidities. All other forms of treatment are more or less empirical. Invasive treatment should be restricted to selected cases and should only be offered in specialized centers. DISCUSSION: If these recommendations are followed the prognosis for CRPS is not as poor as commonly assumed. Whether this means a return to the previous quality of life is unclear and often depends on very personal factors.

Application of local anesthesia inhibits effects of low-energy extracorporeal shock wave treatment (ESWT) on nociceptors.

OBJECTIVE: Clinical studies of extracorporeal shock wave therapy (ESWT) provided conflicting results depending on the use of local anesthesia (LA). DESIGN: The present study investigated whether the biological effects of ESWT differ between application with and without LA. SETTING AND PATIENTS: In 20 healthy subjects, ESWT was applied to the ventral surface of forearm skin, either after topical lidocaine pretreatment or without on the corresponding contralateral side. MEASURES: During and after ESWT ongoing pain, axon-reflex vasodilation (laser Doppler imaging), thresholds for pinprick, and blunt pressure were recorded. RESULTS: The results indicate that increasing ESWT energy flux density led to increasing pain (P < 0.001). LA reduced ESWT-related pain (P < 0.02) and in parallel inhibited local axon-reflex vasodilation (P < 0.001). In addition, LA prevented ESWT-related drop in pressure pain threshold (P < 0.001). CONCLUSION: This study provided evidence that ESWT dose-dependently activates and sensitizes primary afferent nociceptive C-fibers, and that both activation and sensitization were prevented if LA was applied locally. These results suggest that LA substantially alters the biological responses of ESWT.

[Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines]. / Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen. Zusammenfassung der S3-Leitlinie.

Epidural spinal cord stimulation (SCS) is a reversible but invasive procedure which should be used for neuropathic pain, e.g. complex regional pain syndrome I (CRPS) and for mostly chronic radiculopathy in connection with failed back surgery syndrome following unsuccessful conservative therapy. Epidural SCS can also successfully be used after exclusion of curative procedures and conservative therapy attempts for vascular-linked pain, such as in peripheral arterial occlusive disease stages II and III according to Fontaine and refractory angina pectoris. Clinical practice has shown which clinical symptoms cannot be successfully treated by epidural SCS, e.g. pain in complete paraplegia syndrome or atrophy/injury of the sensory pathways of the spinal cord or cancer pain. A decisive factor is a critical patient selection as well as the diagnosis. Epidural SCS should always be used within an interdisciplinary multimodal therapy concept. Implementation should only be carried out in experienced therapy centers which are in a position to deal with potential complications.

Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome.

PURPOSE: Several articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible. RESULTS: Nine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label "CRPS"; 2) the "unclear" pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research. CONCLUSION: The level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients' signs and symptoms.

Functional imaging of sympathetic activation during mental stress.

Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin conductance and heart rate were continuously recorded. The results show that sympathetic activation through mental stress is associated with distinct cerebral regions being immediately involved in task performance (visual, motor, and premotor areas). Other activated regions (right insula, dorsolateral superior frontal gyrus, cerebellar regions) are unrelated to task performance. These latter regions have previously been considered to be involved in mediating different stress responses. The results might furthermore serve as a basis for future investigations of the connection between these cortical regions in the generation of stress-related diseases.

Cortical control of thermoregulatory sympathetic activation.

Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32 degrees C), temperature was either decreased to 7 degrees C (cold), increased to 50 degrees C (warm) or kept constant (32 degrees C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke.

High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid.

BACKGROUND: So far, an inflammation of the central nervous system (CNS) is diagnosed by immunoglobulin measurement in cerebrospinal fluid (CSF) and serum as well as by determination of the oligoclonal bands. With the free kappa and lambda light chains, new markers to diagnose intrathecal synthesis are available. METHODS: In addition to routine diagnostic tests and the assessment of standard parameters, free immunoglobulin light chains were measured in the CSF of patients with neurological disorders. RESULTS: A significant agreement was found between an increase in free kappa light chain CSF serum quotients and results of the currently widely applied method of oligoclonal band measurement for the detection of intrathecal immunoglobulin synthesis. A sensitivity of 95% and 100% specificity for free kappa light chain concentrations at a cut-off of 0.41 mg/l was determined for free kappa light chains compared with oligoclonal bands. However, the free lambda light chains in 20 out of the 110 investigated samples were characterized by inconsistent behaviour. These otherwise unremarkable samples yielded increased CSF quotients, leading to the assumption that free lambda light chains represent a highly sensitive measure of intrathecal immunologlobulin synthesis. Thirteen of the 20 samples described above were obtained from patients with cerebral infarction, 4 samples derived from patients with cerebral paresis (primarily facial paresis), one sample was from a patient with multisystem atrophy and two were obtained from patients with migraine and neuralgia. CONCLUSION: These findings suggest that the high sensitivity of lambda light chains for the detection intrathecal immunoglobulin synthesis may be of benefit in establishing clinical diagnoses.

[Prevalence and risk factors of phantom limb pain and phantom limb sensations in Germany. A nationwide field survey]. / Prävalenz und Risikofaktoren von Phantomschmerzen und Phantomwahrnehmungen in Deutschland. Eine bundesweite Befragung.

BACKGROUND: Data on the incidence and intensity of phantom limb pain (PLP) and phantom limb sensations (PLS) were collected in a nationwide survey. MATERIALS AND METHODS: Supported by a manufacturer of artificial limbs and press notices a total of 537 amputees were contacted and interviewed by questionnaire. RESULTS: The questionnaire containing 62 questions was filled in by 537 out of 1,088 amputees. Of the amputees 14.8% were pain free, 74.5% had PLP, 45.2% stump pain (SP) and 35.5% a combination of both. In addition 62.4% of the amputees reported disturbed sleep, of those with PLP it was even higher at 77.3% and 66.8% of patients with PLP woke up several times during the night. The prevailing features of PLP included burning sensation (13.6%), cramp (15.3%), prickling (23.4%), electrification (21%) and tingling (20.4%). Phantom sensations were felt by 73.4% and were described as being mobile (66.8%), of normal temperature (64%), warm (19.5%), cold (16.5%), bare (35.9%), clothed (13.6%), not unpleasant (31.7%), pressed (29.6%), contorted (7.5%) and blown up (5.8%). Of the patients with PLP, 35.7% described the location as mostly ventral, 26.7% as mostly dorsal. Significantly more PLP was found in the presence of PLS than in its absence (p <0.0001), but unrelated to the type of PLS, to demographic factors, or to the level or side of amputation. Perception of the artificial limb being "a foreign body" was highly significantly more often associated with PLP than with a sensation of "fusing with the body" (p <0.0001). CONCLUSION: To our knowledge the present study constitutes the largest field survey on phantom limb pain carried out in Europe and corroborates the high prevalence and intensity of PLP, unusual PLS and amputation-related sleep disturbances. The significance and manageability of phantom feelings and its risk factors need further research.

Mental load during cognitive performance in complex regional pain syndrome I.

BACKGROUND: Complex regional pain syndrome (CRPS) is associated with deficits in limb recognition. The purpose of our study was to determine whether mental load during this task affected performance, sympathetic nervous system activity or pain in CRPS patients. METHODS: We investigated twenty CRPS-I patients with pain in the upper extremity and twenty age- and sex-matched healthy controls. Each participant completed a limb recognition task. To experimentally manipulate mental load, the presentation time for each picture varied from 2 s (greatest mental load), 4, 6 to 10 s (least mental load). Before and after each run, pain intensity was assessed. Skin conductance was recorded continuously. RESULTS: Patients with CRPS did not differ from controls in terms of limb recognition and skin conductance reactivity. However, patients with CRPS reported an increase in pain during the task, particularly during high mental load and during the latter stages of the task. Interestingly, state anxiety and depressive symptoms were also associated with increases in pain intensity during high mental load. CONCLUSIONS: These findings indicate that high mental load intensifies pain in CRPS. The increase of pain in association with anxiety and depression indicates a detrimental effect of negative affective states in situations of high stress and mental load in CRPS. SIGNIFICANCE: The effects of mental load need to be considered when patients with CRPS-I are investigated for diagnostic or therapeutic reasons.

Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. OBJECTIVES: To define recovery from the patients' perspective and better understand their priorities for treatment approaches. METHODS: Establishing an international consortium, we used a 2-Round Delphi-based study in eight countries across Europe and North America. Participants ≥18 years who met, or had met, Budapest clinical criteria were included. Round 1 participants completed the statement: 'I would/do consider myself recovered from CRPS if/because…' alongside demographic and health questionnaires. Data were thematically organised and represented as 62 statements, from which participants identified and ranked their recovery priorities in Round 2. RESULTS: Round 1 (N = 347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily living; bodily functions; external factors; participation and personal factors. The top five priority statements in Round 2 (N = 252) were: no longer having (1) CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of movement, (4) need for medication, (5) stiffness in the affected limb. With very few exceptions, priorities were consistent, irrespective of patient demographics/geography. Symptoms affecting daily activities were among those most frequently reported. CONCLUSIONS: Our data showed a small number of themes are of highest importance to CRPS patients' definition of recovery. Patients want their pain, movement restriction and reliance on medication to be addressed, above all other factors. These factors should therefore be foremost concerns for future treatment and rehabilitation programmes. SIGNIFICANCE: Those with longstanding CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining recovery is therefore problematic in CRPS. Our study has identified patients' definition of recovery from CRPS, in order of priority, as relief from: their CRPS-related pain, generalised pain, movement restriction, reliance on medication, and stiffness.

Autoimmunity in complex-regional pain syndrome.

Complex regional pain syndrome (CRPS) is an etiologically unclear syndrome with the main symptoms being pain, trophic and autonomic disturbances, and functional impairment that develops after limb trauma or operation and is located at the distal site of the affected limb. Because autoantibodies against nervous system structures have been described in these patients, an autoimmune etiology of CRPS is discussed. These autoantibodies bind to the surface of peripheral autonomic neurons. Using a competitive binding assay, it can be shown that at least some of the CRPS sera bind to the same neuronal epitope. Autoimmune etiology of CRPS is a new pathophysiological concept and may have severe impact on the treatment of this often chronic disease.

Increased prevalence of posttraumatic stress disorder in CRPS.

BACKGROUND: Although specific psychological disorders in complex regional pain syndrome (CRPS) have not been identified, studies suggest that CRPS patients may have increased rates of traumatic life events. Because these events do not always lead to apparent psychological symptoms, we systematically screened CRPS patients for posttraumatic stress disorder (PTSD) to determine if PTSD could be a risk factor for CRPS. METHODS: Consecutive CRPS patients referred to two university hospital centres (University of Erlangen, UMC Mainz) between December 2011 and April 2013 were prospectively examined using a diagnostic PTSD instrument (Post-traumatic Stress Diagnostic Scale (PDS). We also tested maladaptive coping strategies (brief-COPE inventory) and the PDS severity score as predictors for CRPS. Patients with non-CRPS extremity pain and healthy individuals were used as control groups. RESULTS: We collected data from 152 patients with CRPS, 55 control patients and 55 age- and sex-matched healthy individuals. Fifty-eight CRPS patients (38%), six non-CRPS pain patients (10%) and two healthy individuals (4%) met diagnostic criteria for PTSD. Initial PTSD symptom onset was prior to CRPS in 50 CRPS patients (86%) and during the course of CRPS in eight patients. Results of a logistic regression revealed that the PTSD severity score was associated with CRPS (p < 0.0001). Maladaptive coping strategies (p < 0.0001) were related to PTSD. CONCLUSIONS: posttraumatic stress disorder (PTSD) is more frequent in patients with CRPS than it is in the general population. SIGNIFICANCE: Research has not yet provided support for specific psychological predictors for CRPS.

Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain.

BACKGROUND: The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. METHODS: Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 µg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin® , 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin. RESULTS: BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005). CONCLUSION: BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin. SIGNIFICANCE: The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.

Treatment of painful radiculopathies with capsaicin 8% cutaneous patch.

BACKGROUND AND OBJECTIVE: The treatment of neuropathic pain due to low-back (lumbosacral) radiculopathies, a common source of neuropathic pain, is challenging and often requires a multimodal therapeutic approach. The capsaicin 8% patch is the first topical analgesic licensed for peripheral neuropathic pain. To evaluate this treatment, a subset of patients with painful radiculopathy (lumbar and cervical, including ventral and dorsal rami) enrolled into the multicenter, non-interventional QUEPP study (Qutenza 2 - safety and effectiveness in peripheral neuropathic pain) was analyzed. METHODS: Of the 1044 study participants, 50 were diagnosed with painful radiculopathy as only peripheral neuropathic pain syndrome and were eligible for evaluation. Patients received a single treatment (visit 1) with follow-up visits 2-5 at weeks 1-2, 4, 8 and 12. Parameters assessed at all visits included pain intensity, neuropathy symptoms and side effects. Quality of life (SF-12) and painDETECT 1 questionnaires were completed at baseline and final visit. Data was analyzed by patch application site and duration of pain. RESULTS: Topical treatment led to a significant decrease of pain intensity between weeks 1/2 and week 12 versus baseline at the application sites representing dermatomes of ventral (N = 26) and dorsal rami (N = 13) of spinal nerves. A significant decline (p ≤ .001) of numeric pain rating scale scores was observed between weeks 1/2 following patch application and the end of observation (week 12) in the overall radiculopathy group (N = 50), and the groups with either 3 months to 2 years (N = 14) or >2 years (N = 23) duration of pain. Pain relief of at least 30% was observed in 50.0%, 71.4% and 39.1% of patients in the respective groups. Four patients experienced in total seven adverse drug reactions (application site pain or pruritus). CONCLUSION: Effective neuropathic pain relief was observed after patch application within the innervation territories of both dorsal and ventral branches of the spinal nerve. Further controlled randomized trials are indicated.

Quantitative sensory testing: a comprehensive protocol for clinical trials.

We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures. Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyperpathia), and to assess both cutaneous and deep pain sensitivity. The practicality of the QST protocol was tested in 18 healthy subjects, 21-58 years, half of them female. All subjects were tested bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for the presence of 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 (pain to light touch), and pain summation (wind-up ratio) using repetitive pinprick stimulation. The full protocol took 27+/-2.3 min per test area. The majority of QST parameters were normally distributed only after logarithmic transformation (secondary normalization) except for the frequency of paradoxical heat sensations, cold and heat pain thresholds, and for vibration detection thresholds. Thresholds were usually lowest over face, followed by hand, and then foot. Only thermal pain thresholds, wind-up ratio and vibration detection thresholds were not significantly dependent on the body region. There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of individual symptom profiles.