In recent years, regulatory authorities have signaled a willingness to consider real-world evidence (RWE) data to support applications for new claims and indications for pharmaceuticals. Historically, RWE studies have been the domain of prescription drugs, driven by the fact that clinical data on patients are routinely captured in medical records, claims databases, registries, etc. However, RWE reports of nonprescription drugs and supplements are relatively sparse due to methodological gaps in this area. The objective of this narrative review is to identify which RWE methodologies have been used to study nonprescription products. A total of 49 articles were included based on literature searches. Label comprehension studies, used to support prescription-to-nonprescription switches, are useful in determining how nonprescription products will be used; however, they provide no actual clinical data. The most common RWE studies of nonprescription products were cross-sectional surveys, which investigated a broad range of indications and were conducted in an array of settings, including online, by phone, point-of-sale (pharmacy), outpatient clinics, and shopping malls. However, while this type of study is effective for identifying use patterns and attitudes in the general population, recall bias limits the ability to collect safety and effectiveness data. Studies of electronic medical records and claims databases are hampered by incomplete or absent capturing of data on nonprescription products. As a result, most RWE studies to date have provided limited useful information. Although case reports and expert opinion should not be discounted, in the absence of other information they provide few actual data. Novel approaches using smartphone apps and artificial intelligence may provide new opportunities to collect RWE for nonprescription products, but these areas of research are in their infancy. Overall, there is a need to develop standards for execution of RWE studies of nonprescription products in terms of endpoints, study design, and study quality.

INTRODUCTION:Immunocompromised patients are at increased risk for herpes zoster (HZ)-associated complications. Despite standard therapy with systemic antiviral drugs and analgesics, complications are frequently encountered, including generalization of lesions or persistent neuropathic pain, so-called post-herpetic neuralgia (PHN). Given the scarcity of literature and awareness of therapeutic options to improve patient outcomes, especially for vulnerable patient groups, here we describe a strategy based on early intensification of treatment with a varicella zoster virus-specific hyperimmunoglobulin (VZV-IgG), which is approved in the adjuvant treatment of HZ.METHODS:For this case series, we selected four cases of HZ in patients with impaired immunity due to hemato-oncologic disease or immunosuppressive treatment who presented with either existing generalized lesions and/or severe pain or with other risk factors for a complicated HZ course such as PHN. They were considered to be representative examples of different patient profiles eligible for intensification of treatment by the addition of VZV-IgG to virostatic therapy.CASE REPORT:All patients showed a rapid response to combined treatment with VZV-IgG and a virostatic agent. In two patients who had generalized lesions, the formation of new lesions ceased 1 day after VZV-IgG infusion. One patient, with mantle cell lymphoma, achieved complete healing of the lesions 9 days after diagnosis of HZ, a rare occurrence compared to similar cases or cohorts. A patient with HZ in the cervical region showed a good response after a single dose of VZV-IgG. None of the patients developed post-zoster-related complications. Combination therapy of a virostatic agent and VZV-IgG was well tolerated in these four cases.CONCLUSION:This case series demonstrates highly satisfactory treatment effectiveness and tolerability for VZV-IgG in the adjuvant treatment of immunocompromised HZ patients and supports early intensification of HZ therapy in patients at high risk of severe disease progression.

Cancer diagnosis and treatment are drastic events for patients and their families. Besides psychological aspects of the disease, patients are often affected by severe side effects related to the cancer itself or as a result of therapeutic interventions. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of oral or intravenous chemotherapy. The disorder may require dose reduction of chemotherapy and is accompanied by multiple symptoms with long-term functional impairment affecting quality of life (QoL), e.g., sensory and functional deteriorations as well as severe pain. Although CIPN may reverse or improve after termination of the causative chemotherapy, approximately 30–40% of patients are faced with chronicity of the symptoms. Due to the advantages in cancer diagnosis and treatments, survival rates of cancer patients rise and CIPN may occur even more frequently in the future. In this review, we summarize current recommendations of leading national and international societies regarding prevention and treatment options in CIPN. A special focus will be placed on current evidence for topical treatment of CIPN with high-dose capsaicin. Finally, an algorithm for CIPN treatment in clinical practice is provided, including both pharmacologic and non-pharmacologic modalities based on the clinical presentation.

Abstract. Introduction:. Chronic pain is a frequent severe disease and often associated with anxiety, depression, insomnia, disability, and reduced quality of life. This maladaptive condition is further characterized by sensory loss, hyperalgesia, and allodynia. Blue light has been hypothesized to modulate sensory neurons and thereby influence nociception. Objectives:. Here, we compared the effects of blue light vs red light and thermal control on pain sensation in a human experimental pain model. Methods:. Pain, hyperalgesia, and allodynia were induced in 30 healthy volunteers through high-density transcutaneous electrical stimulation. Subsequently, blue light, red light, or thermal control treatment was applied in a cross-over design. The nonvisual effects of the respective light treatments were examined using a well-established quantitative sensory testing protocol. Somatosensory parameters as well as pain intensity and quality were scored. Results:. Blue light substantially reduced spontaneous pain as assessed by numeric rating scale pain scoring. Similarly, pain quality was significantly altered as assessed by the German counterpart of the McGill Pain Questionnaire. Furthermore, blue light showed antihyperalgesic, antiallodynic, and antihypesthesic effects in contrast to red light or thermal control treatment. Conclusion:. Blue-light phototherapy ameliorates pain intensity and quality in a human experimental pain model and reveals antihyperalgesic, antiallodynic, and antihypesthesic effects. Therefore, blue-light phototherapy may be a novel approach to treat pain in multiple conditions.

The new IASP diagnostic criteria for complex regional pain syndrome (CRPS) (aka “the Budapest Criteria”3; Table 1) have improved the diagnostic specificity for CRPS while maintaining good sensitivity. Internationally, these criteria are now in common use. The IASP CRPS Special Interest Group convened a workshop of CRPS experts in Valencia/Spain in September 2019 to review perceived ambiguities in the diagnostic text and issues identified in applying these criteria in both the research and clinical contexts. After this review, workshop attendees discussed and reached a consensus regarding adaptations to the diagnostic taxonomy text. This process resulted in pragmatic updates to CRPS assessment instructions and the associated text in the IASP taxonomy. The wording of the diagnostic criteria themselves was not altered so as to avoid invalidating the criteria. Table 1 - New IASP diagnostic criteria for complex regional pain syndrome (“Budapest criteria”2) (A–D must apply). A. The patient has continuing pain which is disproportionate to any inciting eventB. The patient reports at least one symptom in 3 or more of the categoriesC. The patient displays at least one sign in 2 or more of the categoriesD. No other diagnosis can better explain the signs and symptoms □□□□ Category Symptom (the patient reports a problem) Sign (you can see or feel a problem on examination) 1 “Sensory” Allodynia (to light touch/brush stoke and/or temperature sensation and/or deep somatic pressure and/or joint movement), and/or hyperalgesia (to pinprick) Reported hyperesthesia also qualifies as a symptom□ □ 2 “Vasomotor” Temperature asymmetry and/or skin colour changes and/or skin colour asymmetry □ □ 3 “Sudomotor/oedema” Oedema and/or sweating changes and/or sweating asymmetry □ □ 4 “Motor/trophic” Decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair/nail/skin) □ □ Adapted from https://www.rcplondon.ac.uk/guidelines-policy/complex-regional-pain-syndrome-adults with permission. The results of this meeting were also used as a justification to update the new ICD-11 text regarding CRPS and its diagnosis. This focus on incorporating changes into the ICD-11 was triggered by the current absence of plans to further update the existing CRPS IASP taxonomy. A consensus proposal was sent to WHO for amending ICD-11 CRPS-related text.5 WHO has already accepted some adaptations (marked with # below). Here, we summarise all the proposed changes. The proposed wording of all new text for CRPS in the ICD-11 development version is attached in the web appendix (Online appendix, available at http://links.lww.com/PAIN/B358). Changes concern 3 areas: (a) diagnostic parenting under ICD-11, (b) CRPS subtypes, and (c) the diagnostic procedure. (a) Diagnostic parenting under ICD-11: The current first parent classification of CRPS in the ICD-11 is “focal or segmental autonomic disorder” (ICD-11 BD8A). We consider this classification to be a mistake based on the historic misunderstanding of CRPS as primarily an autonomic disorder. The past 3 decades of CRPS experimental and clinical research clearly demonstrate that this is not the case. We therefore have proposed that the correct parent is “chronic primary pain.” This proposal is also supported by the American Autonomic Society. (b) CRPS subtypes: (i) CRPS II as defined in the IASP criteria is associated with discrete peripheral nerve damage as indicated by neurological examination, electrodiagnostic testing, or other quasi-objective testing. We now clarify that the diagnostic signs of CRPS II must extend beyond any identified injured nerve territory. Nerve lesion itself may cause separate CRPS-concomitant symptoms and signs, including neuropathic pain, paraesthesias, numbness, and autonomic dysfunction restricted to the injured nerve territory. CRPS II should therefore not be classed as a neuropathic pain condition in accordance with current criteria #.4 Diagnostic signs of CRPS I (without discrete nerve damage) and II are identical. The clinical relevance and implications of subgrouping CRPS into these 2 subtypes remain unclear at present.# (ii) We have introduced a third CRPS subtype and have also modified the description of the current diagnostic label CRPS Not Otherwise Specified (NOS) to minimise any confusion with using this latter term. Patients previously documented as having fully met CRPS criteria (either CRPS I or CRPS II, Table 1) but who currently display CRPS features insufficient to fully meet the diagnostic criteria should be classified into the new CRPS subtype, “CRPS with Remission of Some Features.” These patients should not be classified as having CRPS NOS. Notably, a reduction in the number of CRPS diagnostic signs and symptoms does not necessarily constitute an improvement in the lived experience of CRPS; these patients may not have improved pain nor are they usually free of all CRPS-related signs and symptoms. CRPS with Remission of Some Features is a third formal subtype of CRPS, which by necessity overlaps with either CRPS I or II. At what point CRPS changes from being an ongoing condition potentially requiring continued clinical management (ie, CRPS with Remission of Some Features) to being considered resolved is a topic that will need to be addressed in future research. (iii) The term “CRPS-NOS” in the current IASP criteria has been retained exclusively for application to patients who have never been documented to fulfil the new IASP CRPS criteria (Table 1). That is, they now display some but not all features of CRPS required for formal diagnosis, and no other diagnosis better explains the clinical features. (iv) Warm/cold CRPS and early/persistent CRPS are overlapping presentations that are clinically observed. The group did not consider there to be sufficient evidence yet to create formal CRPS subgroups according to these features. However, there was consensus that research and clinical reports should include this information when describing individual patients, study inclusion criteria, or research participants (clinical experience and research suggest that a substantial proportion of individuals who develop acute CRPS improve or resolve, with a smaller subgroup that fails to substantially improve even with standard care. This transition of CRPS to a more prolonged and difficult to manage condition seems to occur during the first 12-18 months after onset, although there is no widely accepted demarcation point for this distinction. The word “persistent” is used here as a descriptive term for this subgroup of prolonged and intractable CRPS. Use of the alternative term “chronic” is preferred by some CRPS experts. However, we note that the term “chronic” is also broadly used across all pain conditions to refer to pain lasting more than 3 months after tissue injury to distinguish it from “acute” pain. To avoid incorrect implications of the word ‘chronic’ to be understood as a >3 months' pain duration in patients with CRPS, the word “persistent” is used to refer to such prolonged CRPS. For clarity, ‘persistent’ does not necessarily indicate the condition will persist indefinitely—a minority of patients with persistent CRPS will naturally improve).# (c) The diagnostic procedure ICD-11 includes additional text to clarify diagnostic terms and procedures. The purpose of that text, pragmatic clarification of the diagnostic process, bears resemblance to that of the IASP taxonomy and associated text (https://www.iasp-pain.org/files/Content/ContentFolders/Publications2/ClassificationofChronicPain/Part_II-A.pdf), which is not currently being updated. This ICD-11 supplemental text has now been updated for CRPS. The following key points are now all implemented (except viii): (i) All patients should be asked systematically about all symptoms listed in the criteria at each formal diagnostic evaluation, even if they have not previously reported certain symptoms. This is recommended because CRPS signs and symptoms are clinically observed to fluctuate over time.# (ii) Clarification of the terms “asymmetry” and “changes” as used in the current IASP CRPS criteria (Table 1): For unilateral CRPS, assess asymmetry by comparing the affected side to the unaffected side. For (much rarer) bilateral and symmetrical CRPS, assess changes in the affected limbs relative to an unaffected limb in the patient or to the limbs of a typical healthy individual. Asymmetry is based on clinical judgment only, rather than any prespecified criteria.# (iii) For evaluating possible spreading of CRPS beyond a single limb, the full diagnostic criteria must be applied to each limb individually. True spreading of CRPS is defined as CRPS that meets full new IASP/ICD-11 diagnostic criteria (Table 1) for multiple limbs—extension of pain alone to other limbs, which is not unusual, in the absence of other CRPS features is not formally considered to be spreading CRPS.# (iv) Hyperalgesia (note that other definitions of hyperalgesia and allodynia exist for use in other chronic pain conditions)4 is a clinical observation in which a painful stimulus evokes more pain than it normally would. The group recommended standard testing for hyperalgesia by comparing the response to a single pinprick applied in the center of the most affected region to the response to an identical pinprick at the corresponding location on the unaffected limb, or an equivalent control site in the case of bilateral CRPS. The test is positive if reported pain is more intense or lasts longer on the affected limb.# (v) Allodynia is a clinical observation in which pain is evoked by a stimulus that is not normally painful. Stimuli used in clinical allodynia assessment can include light touch, vibration, cool or warm temperature, deep tissue or joint pressure in the affected area, or joint movement. Only one of these is required to confirm whether allodynia is present or absent. Suggested clinical assessment procedures are now outlined as below in the revised text: “allodynia to light touch as tested by light manual touch (or brush); allodynia to tissue pressure as assessed by pressure applied to a joint or other tissue using the evaluator's finger with just enough pressure to make the fingernail bed of the evaluator blanch (turn white) (equating to a pressure of below 100g/cm2, and a load of no more than 500 g; this is substantially less than the pressure recommended for the examination of tender points [4 kg/cm2]),6 allodynia to vibration as assessed using a graded tuning fork over bony prominence on the affected limb; allodynia to cool or warm temperature.”# (vi) Temperature asymmetry is assessed in the affected area and compared with the corresponding area on the contralateral extremity, or a suitable control site in the case of bilateral CRPS. Such asymmetry should be obvious to the touch of the dorsum of the hand of the examiner.# (vii) Obvious color asymmetry of a regional nature (ie, hand, foot, knee, or larger region). Please specify the nature of the color changes, eg, red, blue, pale, or mottled.# (viii) A rare limitation of the CRPS diagnostic criteria is noted: In some cases, an objective CRPS diagnostic sign such as color or temperature asymmetry may be observed by the examiner without the patient reporting the corresponding subjective symptom. This may occur, for example, because the patient cannot feel a temperature change, or a color change is difficult to see (this similarly applies to swelling). This situation may result in a patient's diagnostic symptom-category count dropping below the threshold of 3 required for formal diagnosis, despite the patient objectively displaying sufficient clinical features for diagnosis. In these instances, because of the statistical methods on which the IASP criteria were developed and validated, the obvious common-sense approach that ‘signs override symptoms’ (ie, a sign automatically generates a tick also as a symptom) cannot automatically apply. A related challenge arises also where a patient has impaired vision and is therefore unable to ascertain objective color changes; in these rare cases, a pragmatic solution must be found in which common sense prevails. It is hoped that the modified ICD-11 text clarifies important pragmatic aspects of CRPS assessment and diagnosis, and that it will enhance usability of these criteria in both clinical and research settings. All changes and clarifications marked with a # above have already been incorporated into the ICD-11 CRPS text and should be applied in the CRPS diagnostic process immediately. Future research should (1) clarify whether CRPS type 1 and 2 are indeed separate entities or are better merged; (2) assess whether introduction of further subgroups such as warm-cold and early-persistent CRPS is useful (eg, for predicting treatment responses); (3) ascertain the utility of biomarkers for supporting the clinical CRPS diagnosis1; and (4) define “resolved CRPS.” Conflict of interest statement The authors have no conflicts of interest to declare. Appendix A. Supplemental digital content Supplemental digital content associated with this article can be found online at http://links.lww.com/PAIN/B358. Supplemental video content A video abstract associated with this article can be found at http://links.lww.com/PAIN/B329.

Concerning the diagnosis and therapy of pain syndromes, standardized descriptions similar to those used in the examination of psychopathological findings via the system produced by the AMDP ("Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie", i. e., the working group establishing standardized methodology and documentation within psychiatry) are still lacking. Therefore, the authors of this article have founded a working group to establish standardized methodology and documentation for symptoms and signs associated with pain, although not at a diagnosis-specific level, in order to promote standardization in the documentation of pain and rating of the symptoms associated with a given set of medical results. This article presents a system for documenting the symptoms and signs associated with pain globally and independently of the diagnosis (Structured Pain Assessment System) with nomenclature that is inspired by the AMDP system. The objective of this working group is to develop documentation for a uniform multidimensional pain assessment (with defined terminology) that serves as a comparable and unified standard in the field.

Background In a previous study, we reported that selective dorsal root ganglion stimulation (DRG STIM ) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRG STIM -related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRG STIM effects in CRPS patients. Methods Twelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRG STIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area. Results At baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRG STIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRG STIM . Conclusions Selective L4-DRG STIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics. The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267

The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients.

OBJECTIVE:We pursued the hypothesis that complex regional pain syndrome (CRPS) signs observed by neurologic examination display a structure allowing for alignment of patients to particular phenotype clusters.METHODS:Clinical examination data were obtained from 3 independent samples of 444, 391, and 202 patients with CRPS. The structure among CRPS signs was analyzed in sample 1 and validated with sample 2 using hierarchical clustering. For patients with CRPS in sample 3, an individual phenotype score was submitted to k-means clustering. Pain characteristics, quantitative sensory testing, and psychological data were tested in this sample as descriptors for phenotypes.RESULTS:A 2-cluster structure emerged in sample 1 and was replicated in sample 2. Cluster 1 comprised minor injury eliciting CRPS, motor signs, allodynia, and glove/stocking-like sensory deficits, resembling a CRPS phenotype most likely reflecting a CNS pathophysiology (the central phenotype). Cluster 2, which consisted of edema, skin color changes, skin temperature changes, sweating, and trophic changes, probably represents peripheral inflammation, the peripheral phenotype. In sample 3, individual phenotype scores were calculated as the sum of the mean values of signs from each cluster, where signs from cluster 1 were coded with 1 and from cluster 2 with -1. A k-means algorithm separated groups with 78, 36, and 88 members resembling the peripheral, central, and mixed phenotypes, respectively. The central phenotype was characterized by cold hyperalgesia at the affected limb.CONCLUSIONS:Statistically determined CRPS phenotypes may reflect major pathophysiologic mechanisms of peripheral inflammation and central reorganization.

BackgroundTrigeminal neuralgia is difficult to treat and shows upregulation of sodium channels. The expectorant ambroxol acts as a strong local anesthetic, about 40 times stronger than lidocaine. It preferentially inhibits the channel subtype Nav1.8, expressed especially in nociceptive C‐fibers. It seemed reasonable to try ambroxol for the treatment with neuropathic facial pain unresponsive to other standard options.Material and MethodsMedical records of patients suffering from classical trigeminal neuralgia (n = 5) and successful pain reduction following topical ambroxol 20% cream in addition to standard treatment are reported.ResultsAll patients reported pain attacks with pain intensity between 4 and 10 NRS (numeric pain scale). In all cases they could be triggered, 3 patients reported additional spontaneous pain. Attacks were reduced in all 5 patients. Pain reduction achieved following ambroxol 20% cream was 2–8 points (NRS) earliest within 15–30 minutes and lasted for 4–6 hours mostly. This was reproducible in all cases; in one case pain was eliminated after 1 week. No patient reported side effects or skin changes; oral medication was reduced in 2 patients.ConclusionFor the first time, a clinically significant pain relief following topical ambroxol 20% cream in patients with trigeminal neuralgia is reported. In view of the positive side effect profile, topical ambroxol for patients with such a highly impaired quality of life should be investigated further as a matter of urgency.

Hyperalgesia and allodynia are frequent in neuropathic pain. Some pain questionnaires such as the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and the Neuropathic Pain Scale (NPS) include self-assessment or bedside testing of hyperalgesia/allodynia. The aim of this study was to determine to what extent LANSS and NPS data are congruent with findings on quantitative sensory testing (QST). Self-reported presence of dynamic mechanical allodynia (DMA) and descriptors of hot, cold, or deep ongoing pain (the NPS and LANSS) as well as bedside findings of mechanical allodynia (LANSS) were compared with signs of DMA and thermal hyperalgesia on QST in 617 patients with neuropathic pain. Self-reported abnormal skin sensitivity (LANSS) showed a moderate concordance with DMA during bedside test (67.9%, κ = 0.391) or QST (52.8%, κ = 0.165). Receiver operating curve analysis for self-reported DMA yielded similar area-under-the-curve values for the LANSS (0.65, confidence interval: 0.59%-0.97%) and NPS (0.71, confidence interval: 0.66%-0.75%) with high sensitivity but low specificity. Self-reported deep pain intensity was higher in patients with blunt pressure hyperalgesia, but not in patients with DMA or thermal hyperalgesia. No correlations were observed between self-reported hot or cold pain quality and thermal hyperalgesia on QST. Self-reported abnormal skin sensitivity has a high sensitivity to identify patients with DMA, but its low specificity indicates that many patients mean something other than DMA when reporting this symptom. Self-reported deep pain is related to deep-tissue hypersensitivity, but thermal qualities of ongoing pain are not related to thermal hyperalgesia. Questionnaires mostly evaluate the ongoing pain experience, whereas QST mirrors sensory functions. Therefore, both methods are complementary for pain assessment.

Complex regional pain syndrome (CRPS) is a complex pain disorder that can emerge after limb trauma or a lesion in the peripheral nervous system. Typical features include continuing pain, sensory, vasomotor, sudomotor, motor, and trophic changes as well as edema. These signs provide the basis of CRPS diagnosis. A detailed description of the signs, symptoms, and medical history of CRPS could potentially facilitate an earlier and more accurate diagnosis. The aim of this study was to provide such a description, on the basis of epidemiological measures, clinical presentation, and a thorough description of pain sensations. Some signs (eg, differences of skin temperature >1°C), which have been thought to be crucial for diagnosis, were less common than assumed. We identified 11 distinct etiological triggers, which cover more than 99% of the study participants. We developed a weighted score on the basis of the most decisive data, which achieved a sensitivity of .869 and a specificity of .829, compared with .819 and .679 for the Budapest criteria. The weighted diagnostic criteria may help to better aid in distinguishing CRPS from other pain disorders.PERSPECTIVE:This article provides a retrospective epidemiological analysis of 1,043 CRPS patients compared with 421 patients with other pain disorders. The findings could potentially facilitate a more reliable and earlier diagnosis of CRPS, a better differentiation from other pain disorders, and ultimately in a more targeted and effective therapy.

Aim: The secretolytic drug ambroxol may be useful for the treatment of neuropathic pain due to its multiple modes of action. We hypothesized that ambroxol may be a treatment option for complex regional pain syndrome (CRPS). Methods: Additional to standard therapy, eight CRPS-patients with symptoms of less than 12 months were treated with topical 20% ambroxol cream. Clinical courses were assessed using detailed anamnesis and clinical examination. Results: Following treatment we found a reduction of spontaneous pain (6 patients), pain on movement (6 patients), edema (seven patients), allodynia (six patients), hyperalgesia (seven patients), reduction of skin reddening (four patients), improvement of motor dysfunction (six patients) and improvement of skin temperature (four patients). Conclusion: Topical treatment with ambroxol cream may ameliorate symptoms of CRPS.

BACKGROUND:In complex regional pain syndrome (CRPS), altered perception of the affected hand and neglect-like symptoms of the affected body side are common features. In this study, we presented tactile stimuli to the affected hands in CRPS patients and matched healthy controls. METHODS:The participants' task was to point at the perceived positions of the stimuli using a tracking device. The spatial coordinates of the perceived positions were analysed for accuracy and consistency. We also presented patterns consisting of two stimuli at distinct positions with a delay of 100 ms. These patterns are known to induce spatiotemporal integration ("sensory saltation"). RESULTS:CRPS patients were less accurate and less consistent in the spatial perception of tactile stimuli on their hands. Furthermore, they showed increased spatiotemporal integration, although these effects were smaller than expected. These deficiencies were related to the clinically assessed intensity of recurrent pain episodes. Surprisingly, the intensity of clinically assessed ongoing pain was associated with increased precision. CONCLUSIONS:In line with earlier reports, our findings indicate that the representation of the affected hands in CRPS patients is less accurate than in healthy people, probably reflecting reorganization in somatosensory cortices. The exact relationships between these findings and other aspects of CRPS remain to be elucidated. SIGNIFICANCE:CRPS patients performed poorly in localizing positions on their affected hands via pointing and exhibited increased spatiotemporal integration. The presented method may prove useful in diagnostics as well as psychophysical and neurofunctional research on CRPS and other chronic pain disorders.

Objectives: To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain. Methods: A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using “bedside tests” and Brief Pain Inventory (question 5). Results: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12. Conclusions: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

Zusammenfassung Die Autoren stellen als Arbeitsgemeinschaft für Methodik und Dokumentation von Schmerzbefunden (AMDS) ein System zur Befunderhebung vor. Dieses lehnt sich in seiner Struktur an das AMDP-System (System der Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie) zur Dokumentation psychiatrischer Befunde an. Die vorgeschlagenen Merkmale wurden in einem Stufenprozess aus in aktuellen Leitlinien und Klassifikationen verwendeten Begrifflichkeiten zusammengetragen und teilweise in übergeordnete Merkmale integriert. Mit den aus diesem Vorgehen entstandenen Merkmalen soll die Breite verschiedener Schmerzerkrankungen abgebildet werden. Der Schmerzbefund gliedert sich in die Bereiche Algesiomotorik, psychalgesiologischer Befund und somatoalgesiologischer Befund. Ziel ist die Erhebung eines mehrdimensionalen algesiologischen Befunds mit definierten Begrifflichkeiten, der als vergleichbarer und einheitlicher Standard insbesondere im Bereich der Schmerzbegutachtung fungieren kann. Es sollen mit dem AMDS-System systematische Beschreibungen von Schmerzen ermöglicht werden, die als Grundlage von Diagnostik, Therapieplanung und gutachterlicher Fallevaluation dienen.