Quantitative sensory testing (QST). English version.

Quantitative sensory testing (QST) is a standardized and formalized clinical sensitivity test. Testing describes a subjective (psychophysical) method that entails a cooperation of the person to be examined. Within its framework, calibrated stimuli are applied to capture perception and pain thresholds, thus providing information on the presence of sensory plus or minus signs. The presented QST battery imitates natural thermal or mechanical stimuli. The aim is to acquire symptom patterns of sensory loss (for the functioning of the thick and thin nerve fibers) as well as a gain of function (hyperalgesia, allodynia, hyperpathia) with a simultaneous detection of cutaneous and deep tissue sensibility. Most of the tested QST parameters are normally distributed only after a logarithmic transformation (secondary normal distribution)-except the number of paradoxical heat sensations, of cold and heat pain thresholds, and vibration detection thresholds. A complete QST profile can be measured within 1 h. QST is suitable not only for clinical trials but also in practice as a diagnostic method to characterize the function of the somatosensory system-from the peripheral nerve fiber receptor to the projection pathways to the brain.

Long-term opioid therapy of non-cancer pain : Prevalence and predictors of hospitalization in the event of possible misuse.

BACKGROUND: One major concern of long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) is the risk of abuse of prescribed opioids. OBJECTIVE: To examine the prevalence and predictors of opioid use-related hospitalizations and potential abuse of prescribed opioids by persons with LTOT for CNCP in a sample representative of the German statutory health insurance companies. METHODS: Retrospective cross-sectional study in 2014. Anonymized German health claims database, including 4,028,618 insured individuals of 69 German statutory health insurances. Univariate logistic regression models to evaluate demographic and medical characteristics associated with hospital stays and a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents in insured individuals with CNCP receiving LTOT. RESULTS: The prevalence of LTOT for CNCP was 0.8%; 9.9% of these insured individuals received high-dose LTOT (≥120 morphine equivalent mg/day). The 1­year prevalence of hospital stays with a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents was 1.75% of persons with LTOT. These diagnoses were strongly associated with prescriptions of tranquilizers (odds ratio [OR] 3.63; 95% confidence interval [CI] 3.03; 4.36) and moderately associated with diagnosis of depression (OR 2.52; 95% CI 2.12; 3.00) and slightly associated with diagnosis of somatoform pain disorder (OR 1.89; 95% CI 1.56; 2.28) and high-dose LTOT (OR 1.81; 95% CI 1.44; 2.27). DISCUSSION: The study is in line with the recommendations of the German national guidelines on long-term opioid therapy of chronic non-cancer pain (LONTS) to avoid concomitant prescription of tranquilizers for CNCP and to carefully select and monitor patients with depression and somatoform pain disorder.

painPREDICT: first interim data from the development of a new patient-reported pain questionnaire to predict treatment response using sensory symptom profiles.

Objective: Sensory symptom patterns may be useful for predicting treatment response, and, thus, improve individual therapy in patients suffering from neuropathic pain (NeP). Existing screening questionnaires focus predominately on neuropathic mechanisms without consideration of nociceptive mechanisms or mixed pain states. This study aimed to develop a new questionnaire, painPREDICT, using a wide set of patient-reported descriptors potentially associated with neuropathic and nociceptive pain mechanisms, and to explore sensory symptom patterns. Methods: PainPREDICT was constructed based on exploratory (n = 27 patients) and cognitive debriefing interviews (n = 49 patients and nine physicians), across five NeP conditions. The pilot questionnaire was then administered in a non-interventional, cross-sectional, multi-center study to 840 pain patients across the US and Germany. The identification of a sensory symptom pattern was based on hybrid clustering resulting from items standardization followed by principal component analysis. Results: The final questionnaire included 20 items covering: pain intensity, location of pain, course of pain, and sensory symptoms. Most patients participating in the cross-sectional study suffered either from painful diabetic polyneuropathy (n = 330) or radiculopathy (n = 349), fewer from central pain (n = 61) or other types of NeP (n = 100). The hybrid clustering of the new questionnaire data identified three different characteristic sensory symptom profiles in patients with NeP: "Irritable nociceptors", "deafferentation pain", and "pain attacks with nociceptive component". Although some differences in the distribution of the sensory profiles were found, all profiles were represented in all NeP etiology groups. Conclusions: This study set the ground of painPREDICT and showed promising results for its use to categorize patients according to sensory symptom patterns.

[Long-term opioid therapy of non-cancer pain : Prevalence and predictors of hospitalization in the event of possible misuse]. / Langzeitopioidtherapie von nichttumorbedingten Schmerzen : Prävalenz und Prädiktoren von Krankenhausaufenthalten bei möglicher missbräuchlicher Verwendung.

BACKGROUND: One major concern of long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) is the risk of abuse of prescribed opioids. OBJECTIVE: To examine the prevalence and predictors of opioid use-related hospitalizations and potential abuse of prescribed opioids by persons with LTOT for CNCP in a sample representative of the German statutory health insurance companies. METHODS: Retrospective cross-sectional study in 2014. Anonymized German health claims database, including 4,028,618 insured individuals of 69 German statutory health insurances. Univariate logistic regression models to evaluate demographic and medical characteristics associated with hospital stays and a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents in insured individuals with CNCP receiving LTOT. RESULTS: The prevalence of LTOT for CNCP was 0.8%; 9.9% of these insured individuals received high-dose LTOT (≥120 morphine equivalent mg/day). The 1­year prevalence of hospital stays with a diagnosis of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxications by narcotic agents was 1.75% of persons with LTOT. These diagnoses were strongly associated with prescriptions of tranquilizers (odds ratio [OR] 3.63; 95% confidence interval [CI] 3.03; 4.36) and moderately associated with diagnosis of depression (OR 2.52; 95% CI 2.12; 3.00) and slightly associated with diagnosis of somatoform pain disorder (OR 1.89; 95% CI 1.56; 2.28) and high-dose LTOT (OR 1.81; 95% CI 1.44; 2.27). DISCUSSION: The study is in line with the recommendations of the German national guidelines on long-term opioid therapy of chronic non-cancer pain (LONTS) to avoid concomitant prescription of tranquilizers for CNCP and to carefully select and monitor patients with depression and somatoform pain disorder.

[Drug therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Medikamentöse Therapie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A literature search for systematic reviews of randomized controlled drug trials from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Amitriptyline and duloxetine are recommended in the case of comorbid depressive disorders or generalized anxiety disorder and pregabalin in the case of generalized anxiety disorder. Off-label use of duloxetine and pregabalin can be considered if there are no comorbid mental disorders or no generalized anxiety disorder. Strong opioids are not recommended.

[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 .

[Structure of pain management facilities in Germany : Classification of medical and psychological pain treatment services-Consensus of the Joint Commission of the Professional Societies and Organizations for Quality in Pain Medicine]. / Struktur der schmerzmedizinischen Versorgung in Deutschland : Klassifikation schmerzmedizinischer Einrichtungen - Konsens der Gemeinsamen Kommission der Fachgesellschaften und Verbände für Qualität in der Schmerzmedizin.

On behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.

A retrospective analysis of the long-term test-retest stability of pain descriptors of the painDETECT questionnaire.

OBJECTIVE: PainDETECT (PD-Q) is a patient reported screening questionnaire to identify patients with neuropathic pain based on questions regarding typically sensory symptoms of neuropathic pain. The aim of the present investigation was to assess the test-retest stability of pain descriptors of the PD-Q within a time window of 1-3 weeks. METHODS: Data sets of 74 chronic pain patients sampled in an open pain register at two visits were analyzed and compared. Patients with change of pain localization between visits were excluded from analysis. Beside conventional measures (Pearson correlation coefficient r, intraclass correlation coefficient ICC, kappa), also calculated measures known from method comparison were used. RESULTS: The mean duration between visits was 15 days. The measures were in the range of r = 0.72-0.86, ICC = 0.71-0.86, and kappa = 0.62-0.72 for PD-Q pain descriptors (burning, prickling, mechanical allodynia, pain attacks, thermal hyperalgesia, numbness, pressure induced pain). CONCLUSION: The individual PD-Q pain descriptors showed accurate test-retest stability as a prerequisite for use in repeated measurements (e. g. post baseline or follow up data) in clinical trials.

Are there different predictors of analgesic response between antidepressants and anticonvulsants in painful diabetic neuropathy?

BACKGROUND: To investigate baseline demographics and disease characteristics as predictors of the analgesic effect of duloxetine and pregabalin on diabetic peripheral neuropathic pain (DPNP). METHODS: Based on data from the COMBO-DN study, a multinational clinical trial in DPNP, the potential impact of baseline characteristics on pain relief after 8-week monotherapy with 60 mg/day duloxetine or 300 mg/day pregabalin was assessed using analyses of covariance. Subgroups of interest were characterized regarding their baseline characteristics and efficacy outcomes. RESULTS: A total of 804 patients were evaluated at baseline. A significant interaction with treatment was observed in the mood symptom subgroups with a larger pain reduction in duloxetine-treated patients having no mood symptoms [Hospital Anxiety and Depression Scale (HADS) depression or anxiety subscale score <11; -2.33 (duloxetine); -1.52 (pregabalin); p = 0.024]. There were no significant interactions between treatment for subgroups by age (<65 or ≥65 years), gender, baseline pain severity [Brief Pain Inventory Modified Short Form (BPI-MSF) average pain <6 or ≥6], diabetic neuropathy duration (≤2 or >2 years), baseline haemoglobin A1c (HbA1c) (<8% or ≥8%), presence of comorbidities and concomitant medication use. CONCLUSIONS: Our analyses suggest that the efficacy of duloxetine and pregabalin for initial 8-week treatment in DPNP was consistent across examined subgroups based on demographics and disease characteristics at baseline except for the presence of mood symptoms. Duloxetine treatment appeared to be particularly beneficial in DPNP patients having no mood symptoms.

[Recommendations of the updated LONTS guidelines. Long-term opioid therapy for chronic noncancer pain]. / Empfehlungen der aktualisierten Leitlinie LONTS. Langzeitanwendung von Opioiden bei chronischen nicht-tumorbedingten Schmerzen.

BACKGROUND: The regular update of the German S3 guidelines on long-term opioid therapy for chronic noncancer pain (CNCP), the"LONTS" (AWMF registration number 145/003), began in November 2013. METHODS: The guidelines were developed by 26 scientific societies and two patient self-help organisations under the coordination of the Deutsche Schmerzgesellschaft (German Pain Society). A systematic literature search in the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Scopus databases (up until October 2013) was performed. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. The strength of the recommendations was established by multistep formal procedures, in order to reach a consensus according to German Association of the Medical Scientific Societies ("Arbeitsgemeinschaft der Wissenschaftlich Medizinischen Fachgesellschaften", AWMF) regulations. The guidelines were reviewed by the Drug Commission of the German Medical Association, the Austrian Pain Society and the Swiss Association for the Study of Pain. RESULTS: Opioids are one drug-based treatment option for short- (4-12 weeks), intermediate- (13-25 weeks) and long-term (≥ 26 weeks) therapy of chronic osteoarthritis, diabetic polyneuropathy, postherpetic neuralgia and low back pain. Contraindications are primary headaches, as well as functional somatic syndromes and mental disorders with the (cardinal) symptom pain. For all other clinical presentations, a short- and long-term therapy with opioid-containing analgesics should be evaluated on an individual basis. Long-term therapy with opioid-containing analgesics is associated with relevant risks (sexual disorders, increased mortality). CONCLUSION: Responsible application of opioid-containing analgesics requires consideration of possible indications and contraindications, as well as regular assessment of efficacy and adverse effects. Neither an uncritical increase in opioid application, nor the global rejection of opioid-containing analgesics is justified in patients with CNCP.

[Quantitative sensory testing]. / Quantitative sensorische Testung.

Quantitative sensory testing (QST) is a standardized and formalized set of clinical sensitivity tests based on subjective (psychophysical) methods, which depends on the cooperation of the subject being investigated. Calibrated stimuli are used to measure the perception and pain thresholds, which provide information on the presence of sensory plus or minus signs. The QST equipment presented mimics natural thermal or mechanical stimuli. The rationale is to test for patterns of functional sensory loss or gain by simultaneous assessment of both cutaneous and deep pain sensitivity. The majority of QST parameters are normally distributed only after logarithmic transformation (i.e. secondary normalization). With QST a complete somatosensory profile can be obtained within 1 h. The QST is a suitable method for characterizing the function of the somatosensory system in clinical trials and also in clinical practice as a diagnostic procedure.

Duloxetine use in chronic painful conditions--individual patient data responder analysis.

BACKGROUND: Duloxetine has been studied in four distinct chronic pain conditions - osteoarthritis (OA), fibromyalgia, chronic low back pain (CLBP) and diabetic peripheral neuropathic pain (DPNP). These trials have involved large numbers of patients with at least moderate pain, and have used similar methods for recording pain intensity, over about 12 weeks. METHODS: Data from the trials were pooled according to painful condition, and reanalysed at the level of the individual patient and using increasing levels of pain intensity reduction (<15%, 15-29%, 30-49%, ≥ 50%), with different imputation methods on withdrawal. RESULTS: The proportion of patients recording at least 50% pain intensity reduction plateaued after 2-6 weeks in fibromyalgia, and 8-12 weeks in other conditions. The duloxetine-specific benefit [number needed to treat (NNT) for at least 50% pain intensity reduction] was fairly constant after about 2 weeks for DPNP and fibromyalgia and after about 4 or 5 weeks for OA and CLBP. In all conditions, responses were bimodal, with patients generally experiencing either very good or very poor pain relief. Last-observation-carried-forward imputation produced numerically and occasionally statistically better (lower) NNTs than use of baseline-observation-carried-forward (true response). CONCLUSIONS: Baseline-observation-carried-forward (true response), which combines the success of high levels of pain relief with the failure to experience pain relief on withdrawal of the drug is conservative and probably reflective of clinical practice experience. The distribution of effect was not normal; few patients had the average response and averages are not an appropriate descriptor for these data.

[Current therapy of neuropathic pain]. / Aktuelle Therapie neuropathischer Schmerzen.

Lesions of the nervous systems often result in difficult to treat pain syndromes. Neuropathic pain has increasingly gained attention from clinicians as a result of a better understanding of the underlying mechanisms and the development of proven analgesic therapies. This article provides an update on the diagnosis and treatment of neuropathic pain.

Itch and the brain.

The sensation of itch - defined as unpleasant sensation inducing the urge to scratch - is processed by a network of different brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational patterns. Patients with atopic eczema show different activation patterns and kinetics compared to healthy volunteers. This review summarizes current studies investigating itch in the brain.

[Fibromyalgia syndrome. Definition, classification, clinical diagnosis and prognosis]. / Das Fibromyalgiesyndrom. Definition, Klassifikation, klinische Diagnose und Prognose.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: The clinical diagnosis of FMS can be established by the American College of Rheumatology (ACR) 1990 classification criteria (with tender point examination), by the modified preliminary diagnostic ACR 2010 criteria or by the diagnostic criteria of the German interdisciplinary guideline (AWMF) on FMS. The English full-text version of this article is available at SpringerLink (under "Supplemental").

[Etiology and pathophysiology of fibromyalgia syndrome]. / Ätiologie und Pathophysiologie des Fibromyalgiesyndroms.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. RESULTS: Current data do not identify distinct etiologic or pathophysiological factors mediating development of FMS. The development of FMS is associated with inflammatory rheumatic diseases (EL2b), with gene polymorphisms of the 5-hydroxytryptamine (HT)(2) receptor (EL3a), lifestyle factors (smoking, obesity, lack of physical activity; EL2b), physical and sexual abuse in childhood and adulthood (EL3a). CONCLUSION: FMS is most likely the result of various pathogenetic factors and pathophysiological mechanisms. The English full-text version of this article is available at SpringerLink (under "Supplemental").

[Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Medikamentöse Therapie des Fibromyalgiesyndroms. Systematische Übersicht und Metaanalyse.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder. Strong opioids are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

[Placebo responders in randomized controlled drug trials of fibromyalgia syndrome : Systematic review and meta-analysis]. / Placeboresponder in randomisierten, kontrollierten Medikamentenstudien des Fibromyalgiesyndroms : Systematische Übersicht und Metaanalyse.

BACKGROUND: The superiority of true drug treatment over placebo in reducing symptoms of fibromyalgia syndrome (FMS) is small. Drug placebo treatment of functional somatic syndromes (FSS) such as FMS has been discussed. We determined the magnitude of placebo responders in drug trials with FMS patients to substantiate further research on placebo treatment of FSS. MATERIAL AND METHODS: CENTRAL, MEDLINE, Scopus, and the databases of the U.S. National Institutes of Health and the Pharmaceutical Research and Manufacturers of America were searched for randomized, double-blind, placebo-controlled trials with a parallel design and treatment duration of ≥ 12 weeks in FMS patients from inception to 31 December 2010. The magnitude of placebo responders was assessed by the pooled estimate of patients with a 30% and 50% reduction in pain. RESULTS: Thirty studies with 3,846 patients on placebo were included. The pooled estimate of a 30% placebo pain reduction was 30.8% (95% confidence interval (CI) 29.4-32.3%) and of a 50% placebo pain reduction was 18.8% (95% CI 17.5-20.1%). The pooled estimate of the risk ratio of 30% pain reduction by true drug versus placebo was 1.38 (95% CI 1.27-1.49). The pooled estimate of the risk ratio of 50% pain reduction by true drug versus placebo response was 1.57 (95% CI 1.36-1.81). CONCLUSION: The magnitude of responders to placebo in drug trials of FMS is substantial. The efficacy, safety, and costs of drugs recommended for FMS therapy and open-label placebo should be compared in large multinational trials sponsored by public institutions. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.