[Interdisciplinary multimodal assessment : Interprofessional interaction in team meetings and final talks]. / Interdisziplinäres Multimodales Assessment : Interprofessionelle Interaktion in Teamsitzung und Abschlussgespräch.

BACKGROUND: In PAIN2020 (Innovation Fund, 01NVF17049), an outpatient interdisciplinary multimodal assessment (IMA) was introduced early in the course of the disease. The central quality feature is the close interdisciplinary collaboration of pain medicine, physiotherapy and psychology, which requires a complex organizational and coordination process, especially in team meetings and final discussions. OBJECTIVES: The (different) views of the professional groups involved are brought together in the team process as a common consensus. The process of shaping the interaction of the professional groups among each other in the team meeting and final discussion as well as with the patients is examined (qualitatively) and discussed. METHODS: In PAIN2020, a workshop on IMA was held to jointly reflect on the insights and experiences gained in the process so far through monitoring with staff or teams of the PAIN2020 centers. In one of three work phases, interprofessionally composed groups gathered statements from participants on the design of the interaction in team meeting and final discussion in three rotating rounds within the framework of a World Café. RESULTS: It was possible to identify conducive and obstructive factors for the design of interdisciplinary collaboration in team meetings and final discussions, which were brought together in a superordinate framework model. DISCUSSION: The provision of the new care service as an interdisciplinary task in a team goes beyond existing structural and process parameters in the definition of framework conditions in interdisciplinary multimodal pain therapy and should therefore also take personal competencies and professional competencies into account. Therefore, new dimensions arise for the implementation of the IMA, which should be discussed in the future.

[Feasibility of the interdisciplinary multimodal assessment-The team perspective]. / Umsetzbarkeit des interdisziplinären multimodalen Assessments ­ die Teamperspektive.

BACKGROUND: Secondary preventive outpatient diagnostic services for patients with pain and risk factors for chronification have not yet been sufficiently established. In the PAIN2020 project (Innovation Fund, 01NVF17049) an outpatient interdisciplinary multimodal assessment (IMA) was introduced for the first time early in the course of the disease. OBJECTIVE: For the implementation of the IMA procedures for team cooperation and decision criteria were developed, which were implemented by a team of medical, physiotherapeutic and psychological therapists. These procedures and decision criteria are to be discussed against the background of clinical experience and examined with respect to their feasibility (qualitative). METHODS: In PAIN2020 a workshop on IMA was held in September 2021 to jointly reflect on the findings and experiences gained in the process so far through monitoring and structuring documentation in the implementation with staff or teams of PAIN2020 centers on the feasibility of implementing a structured interdisciplinary multimodal assessment. In three work phases, occupational group-specific and cross-occupational group topics were addressed. RESULTS: In the decision-making processes of the occupational groups, in addition to profession-specific focal points within the framework of the assessment of findings (somatic, functional or psychosocial core criteria), overarching core criteria within the professions as well as complementary patient-related aspects are evident, which are included in the integrative team process. With respect to team collaboration, the implementation of the team meeting and the final discussion can be used to identify structural and process parameters that promote or inhibit implementation, which are also accompanied by interactional factors. DISCUSSION: For the implementation of the IMA, there were (1) adaptations of the IMA, which is currently implemented as A­IMA in the selective agreement with BARMER and (2) new dimensions or task fields and ideas for evidence-based concepts for the content design of integrative diagnostics as well as for the feedback of the results to the patients, which should be discussed in the future.

Pain chronification impacts whole-brain functional connectivity in women with hip osteoarthritis during pain stimulation.

OBJECTIVE: Previous neuroimaging studies have shown that patients with chronic pain display altered functional connectivity across distributed brain areas involved in the processing of nociceptive stimuli. The aim of the present study was to investigate how pain chronification modulates whole-brain functional connectivity during evoked clinical and tonic pain. METHODS: Patients with osteoarthritis of the hip (n = 87) were classified into 3 stages of pain chronification (Grades I-III, Mainz Pain Staging System). Electroencephalograms were recorded during 3 conditions: baseline, evoked clinical hip pain, and tonic cold pain (cold pressor test). The effects of both factors (recording condition and pain chronification stage) on the phase-lag index, as a measure of neuronal connectivity, were examined for different frequency bands. RESULTS: In women, we found increasing functional connectivity in the low-frequency range (delta, 0.5-4 Hz) across pain chronification stages during evoked clinical hip pain and tonic cold pain stimulation. In men, elevated functional connectivity in the delta frequency range was observed in only the tonic cold pain condition. CONCLUSIONS: Across pain chronification stages, we found that widespread cortical networks increase their synchronization of delta oscillations in response to clinical and experimental nociceptive stimuli. In view of previous studies relating delta oscillations to salience detection and other basic motivational processes, our results hint at these mechanisms playing an important role in pain chronification, mainly in women.

[Clinical updates on phantom limb pain : German version]. / Klinisches Update zu Phantomschmerz : Deutsche Fassung.

INTRODUCTION: Most patients with amputation (up to 80 %) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. METHODS: This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. RESULTS: The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. DISCUSSION: Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

[Development of two outpatient interdisciplinary group modules in the treatment of patients with pain and risk of chronification]. / Entwicklung zweier ambulanter gruppentherapeutischer interdisziplinärer Therapiemodule in der Behandlung von Patienten mit Schmerzen und Chronifizierungsrisiko.

BACKGROUND AND OBJECTIVE: An early treatment of patients who suffer from pain and show risk factors for chronification is meaningful as these patients can benefit from an early interdisciplinary multimodal pain treatment (IMST). In view of the insufficient treatment, two outpatient treatment modules for the secondary prevention of pain chronification are developed within the framework of PAIN2020: the educative and accompanying IMST (E­IMST and B­IMST). MATERIAL AND METHODS: The developmental process of both IMSTs is presented. In this context two target groups of patients were defined for which 1 session (E­IMST) or 10 intervention appointments (B­IMST) were planned, depending on the chronification, impairment and complexity of the disorder. The conception was carried out in five steps: development of the objectives, development of the main contents, workshop on the content and conceptional design (contents, mediation, exercises), preparation of a time schedule and processing of the results (manual, presentations, worksheets, handbook). The B­IMST was initially developed from which the contents for the E­IMST were subsequently extracted. Additionally, a concept for testing the feasibility and a working model for a pilot study were developed. RESULTS: The objectives for both forms of IMST are improvement of the understanding of pain and contributing factors, the increase of the experience of control and self-efficacy and the increase in self-responsibility with respect to strategies to reduce pain. Differences between the two treatment modules arise from the needs and framework conditions. Medical, physiotherapeutic and psychotherapeutic contents and schedules were organized for both IMST modules. The B­IMST consists of five modules each with two sessions as group interventions (biopsychosocial model, activation planning, regulation of needs, sleep and medication, routine transfer). The 3­h E­IMST group intervention mainly intends to mediate knowledge on pain and the biopsychosocial pain model. Theoretical and practical interventions, empirical knowledge and experience-oriented methods are employed. CONCLUSION: There are now two interdisciplinary structured manuals for the secondary preventive treatment of patients with recurrent pain and a risk profile for chronification. These approaches must now prove themselves with respect to feasibility and effectiveness.

Cross-cultural adaptation and validation of the German Central Sensitization Inventory (CSI-GE).

BACKGROUND: The Central Sensitization Inventory (CSI) is a screening tool designed to detect symptoms related to Central Sensitization (CS) and Central Sensitivity Syndromes (CSS) by measuring the degree of related phenomena. The objective of this study was to create a German, culturally-adapted version of the CSI and to test its psychometric properties. METHODS: A German version of the CSI (CSI-GE) was developed, culturally-adapted, and pretested for comprehensibility. The psychometric properties of the resulting version were validated in a clinical study with chronic pain and pain-free control subjects. To assess retest reliability, the CSI-GE was administered twice to a subgroup of patients. Structural validity was tested using factor analyses. To investigate construct validity a hypotheses testing approach was used, including (1) correlations between the CSI-GE and several other well-established questionnaires as well as (2) an investigation of the CSI-GE discriminative power between different subgroups of participants believed to have different degrees of CS. RESULTS: The CSI-GE showed excellent reliability, including high test-retest characteristics. Factor analyses confirmed a bi-factor dimensionality as has been determined previously. Analysing construct validity 6 out of 11 hypotheses (55%) were met. CSI-GE scores differentiated between subgroups according to expectations. Correlations between CSI-GE scores and other questionnaires suggested that none of the correlated constructs was identical, but there was overlap with other questionnaires based on symptom load. Several correlations did not fit with our current understanding of CS. CONCLUSION: The CSI-GE appears to be a reliable tool for measuring CS/CSS-related symptomatology. Whether this implies that the CSI-GE measures the degree of CS within an individual subject remains unknown. The resulting score should be interpreted cautiously until further clarification of the construct.

The virtue of optimistic realism - expectation fulfillment predicts patient-rated global effectiveness of total hip arthroplasty.

BACKGROUND: Emerging evidence highlights the importance of preoperative expectations in predicting patient-reported outcomes of orthopedic surgeries. To date, it is still a matter of controversy whether patient satisfaction can be maximized by promoting either optimistic or realistic outcome expectations before surgery. Adjusting overly optimistic outcome expectancies in favor of a more realistic outlook on the limitations of total hip arthroplasty could reduce the risk of disappointment and lead to greater satisfaction with surgery outcomes. Our prospective cohort study was aimed at comparing the relative predictive influence of baseline expectations, expectation fulfillment and symptomatic improvement on the global effectiveness of total hip arthroplasty. METHODS: Ninety patients (49 female, 41 male; mean age: 63 ± 12.87 years) fulfilled inclusion criteria and completed a comprehensive preoperative assessment comprising sociodemographic, clinical, functional and psychological phenotypes. Moreover, the strengths of preoperative expectations for improvements in eight pain-related and functional domains were recorded on a 5-point Likert-scale. At 12 months after surgery, patients were asked to rate perceived improvements in each of these domains as well as the global effectiveness of the total hip replacement on a 5-point Likert-scale. To evaluate the relative impact of preoperative expectations, symptom improvement and the fulfillment of expectations on the global effectiveness of surgery, a sequential multiple regression analysis was performed. RESULTS: Compared with the actual improvement at 12-months follow-up, prior expectations had been overly optimistic in about 28% of patients for hip pain, in about 45% for walking ability and around 60% for back pain, independence in everyday life, physical exercise, general function social interactions and mental well-being. An optimistic hip pain expectation, walking ability at baseline and the fulfillment of expectations for walking ability, general function and independence in everyday life were found to independently predict global effectiveness ratings. CONCLUSIONS: Positive expectation about pain and the fulfillment of expectations concerning functional domains predicted higher global effectiveness ratings. In line with many authors investigating the relationship between the fulfillment of expectations and satisfaction with medical interventions, we suggest that professionals should explicitly address their patients' expectations during the preoperative education and consultation.

[Prevention of chronic pain in the German healthcare system : Current state and perspective]. / Vermeidung chronischer Schmerzen in der deutschen Gesundheitsversorgung : Derzeitiger Stand und Ausblick.

The current healthcare provision in Germany is established, in particular, for the diagnostics and treatment of chronic pain conditions; however, the current aim is to initiate the diagnostic and therapeutic approaches oriented towards the biopsychosocial pain model in the early stages of pain, i.e. before the onset of chronification, for patients with pain and a risk of chronification in order to actively avoid chronification processes. In this context, multiple risk factors play an important role for the diagnostic and therapeutic approaches as well as for the interdisciplinary multimodal pain therapy developed for this purpose. The Global Year of the International Association for the Study of Pain (IASP) 2020 addressed the prevention of (chronic) pain, a welcome opportunity to provide a short review of the evidence for and clinical experiences with timely diagnostic and therapeutic options and to summarize the current framework conditions and scientific recommendations for Germany. At the end of this article the implications for future research are summarized, particularly for the treatment of patients with pain and risk of chronification.

[Evaluation of an early interdisciplinary multimodal assessment for patients with pain : Protocol of a randomized controlled study (PAIN2020)]. / Evaluation eines frühen interdisziplinären multimodalen Assessments für Patienten mit Schmerzen : Protokoll einer randomisierten kontrollierten Studie (PAIN2020).

Health care provision for patients with pain and risk factors for chronicity is still insufficient and characterized in particular by over-, under- and misuse of existing approaches. The PAIN2020 project is funded by the German Federal Ministry of Health Care (Innovationsfonds 01NVF17049) and aims to improve health care delivery for this group of patients by implementing an early ambulatory diagnostic approach by a pain specialist, resulting in an improvement in pain and restored or maintained function. A randomized clinical trial in 31 facilities Germany-wide will identify eligible patients and guide them into early specialized pain diagnostics. The interventional arm provides an interdisciplinary multimodal assessment, delivered by pain medicine specialists, physiotherapists and clinical psychologists. The control arm contains a single assessment by a pain specialist. Patients and caregivers receive detailed recommendations for evidence-based interventions tailored to the needs of the individual patient. Two evaluation approaches will be merged. The first requires a net sample size of 3840 patients, assessed (admission) and followed-up (3 and 6 months) by clinical data (German Pain Questionnaire, additional scales) and analyzed by a multi-level approach. In a second evaluation arm the clinical data of the included patients will be supplemented by secondary data from a statutory health insurance (BARMER) and compared to a sample of policyholders not addressed by the study. Data analyses will be performed by an external evaluation institute. The project started in April 2018.

[Pain Management in Hospitals - Current Practice, Quality and Organisation in Non-surgical Medical Care]. / Schmerzmanagement im Krankenhaus ­ aktuelle Praxis, Qualität und Organisation in der nichtoperativen Medizin.

For many years now, effective pharmacological and non-pharmacological treatment approaches for acute and chronic pain exist, as well as organisational strategies for their implementation in hospitals. Nevertheless, there remain considerable deficits in pain management and the portion of patients with severe or long-lasting pain in non-surgical units is often high. There is a considerable potential to improve quality and structures of pain mangement in non-surgical hospital settings in Germany. Recently, legal requirements to establish a structured perioperative pain management were introduced. This should not be seen as a signal that pain management is less important in non-surgical disciplines. On the contrary - it should raise awareness for more clinical and health services research to further develop and validate appropriate approaches and concepts to improve pain treatment in this field.

[Pain Management in Non-surgical Inpatients - Treatment Approaches and Competence for Pain Services]. / Schmerztherapie bei nichtoperativen Patienten im Krankenhaus ­ Therapieansätze und Behandlungskompetenz im Schmerzdienst.

The number of non-surgical patients in the hospital setting with pain due to medical conditions or comorbidities and/or invasive procedures or treatments is high. Compared to perioperative pain management, the portion of patients and/or conditions that require more than an approach focused on pharmacological treatment of nociceptive pain is considerably higher. Rather, treatment often requires the differentiated use of co-analgesics, non-pharmacological treatments, physiotherapy, occupational therapy, psychological assessment and interventsions and educational approaches, ideally in the form of closely coordinated interdisciplinary treatment. The assessment and treatment of acute and especially chronic pain should follow the biopsychosocial concept of pain, especially if risk factors for chronification have been identified, if patients receive high-dose therapy with analgesics or have preexisting a chronic pain disorder.

[Method report of the second update of the guidelines on long-term opioid therapy for chronic noncancer pain]. / Leitlinienreport der zweiten Aktualisierung der S3-Leitlinie "Langzeitanwendung von Opioiden bei nicht-tumorbedingten Schmerzen ­ LONTS".

BACKGROUND: The update of the German S3 guidelines on long-term opioid therapy of chronic noncancer pain (CNCP), the LONTS (AWMF registration number 145/003), was scheduled for February 2020 due to the expiry of the validity period. METHODS: The guidelines were updated by 28 scientific societies and 2 patient self-help organizations under the coordination of the German Pain Society and the Association of the Scientific Medical Societies in Germany (AWMF). RESULTS: A systematic literature search was performed in the CENTRAL, MEDLINE and Scopus databases from October 2013 to December 2018. The previous meta-analyses of randomized controlled trials (RCT) of opioids in CNPC syndromes with a study duration of ≥4 weeks were updated. Levels of evidence were assigned according to the Oxford Centre for Evidence-Based Medicine version 2009 classification system. The formulation and strength of recommendations was established in a multistep formalized consensus procedure, in accordance with AWMF rules and standards. The guidelines were reviewed by four experts not involved in the development of the guidelines. The public was given the opportunity to comment on the guidelines. The guidelines were approved by the executive boards of the societies that were engaged in development of the guidelines. CONCLUSION: The guidelines will be published in several forms: complete and short scientific versions as well as clinical practice and patient versions.

[Quality improvement in conservative pain management (QUIKS) : A module of the QUIPS project for benchmarking of pain treatment in patients with nonoperative care]. / Qualitätsverbesserung im konservativen Schmerzmanagement (QUIKS) : Ein Modul des QUIPS-Projekts zum Benchmarking der Schmerztherapie bei Patienten der nichtoperativen Versorgung.

BACKGROUND: National and international surveys have shown that the quality of pain therapy in hospitals shows deficits, especially in the nonoperative disciplines. OBJECTIVE: The objective was to develop and clinically validate a module for the outcome and process parameters for pain management in patients in the context of a conservative/nonoperative hospital treatment analogous to the QUIPS questionnaire (quality improvement in postoperative pain therapy), which focuses on postoperative pain management. MATERIAL AND METHODS: In a 4-step procedure the QUIPS outcome questionnaire and the process assessment sheet of the QUIPS module were adapted to the conditions of conservative/nonoperative treatment. Patients from internal medicine, neurology and dermatology took part in the systematic testing and the clinical validation. RESULTS: A total of 973 patients were enrolled (inclusion rate 74%, n = 403 internal medicine, n = 401 neurology, n = 169 dermatology). The majority completed the questionnaire independently while 33% of the patients needed support, which was given in the form of an interview. Apart from a few deficits, most questions about pain intensity and function were fully recorded. The evaluation of the outcome was difficult as regardless of the pain therapy, a relevant proportion of the patients reported no pain. Due to the lack of conclusive diagnoses at the time of the assessment, organ-related disease groups were developed using word diagnoses instead of the OPS coding used in QUIPS. CONCLUSION: In addition to the perioperative modules of QUIPS, QUIKS (quality improvement in conservative pain management), an instrument for quality assurance of pain treatment in patients in nonoperative disciplines, is now available.

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

BACKGROUND: The second scheduled update of the German S3 guidelines on long-term opioid therapy for chronic noncancer pain (CNCP), the LONTS (AWMF registration number 145/003), was started in December 2018. METHODS: The guidelines were developed by 28 scientific societies and 2 patient self-help organizations under the coordination of the German Pain Society. A systematic literature search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Scopus databases (up until December 2018) was performed. The systematic reviews with meta-analyses of randomized controlled trials with opioids for CNCP from the previous versions of the guideline were updated. 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 formal multistep procedures in order to reach a consensus according to the Association of the Medical Scientific Societies in Germany (AWMF) regulations. The guidelines were reviewed by four external pain physicians. Public comments were possible for 4 weeks. RESULTS: Opioid-based analgesics are a drug-based treatment option for short-term (4-12 weeks), intermediate-term (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. Based on a clinical consensus the guidelines list other medical conditions for which a therapy with opioids can be considered on an individual basis. Long-term therapy of CNCP with opioids is associated with relevant risks. CONCLUSION: A responsible administration of opioids requires consideration of possible indications and contraindications as well as regular assessment of efficacy and adverse effects. Opioids remain a treatment option for CNCP if nonpharmacological therapies are not effective and/or other drugs are not effective, are not tolerated or are contraindicated.

The Extent of Pain Is Associated With Signs of Central Sensitization in Patients With Hip Osteoarthritis.

BACKGROUND: Central sensitization may be present in some patients with hip osteoarthritis (OA), often reflected as widespread pain. We examine the association between pain extent with signs of central sensitization and other clinical and psychological features in patients with hip OA. METHODS: Thirty patients with hip OA were recruited for this cross-sectional observational study. Participants completed pain drawings on a digital tablet, which displayed frontal and dorsal views of the body. The pain extent (%) for each participant was determined by combining the frontal and dorsal pixels shaded and dividing by the total pixels of the body chart area. Participants completed patient-reported outcome measures to assess for signs and symptoms of central sensitization and psychosocial factors. Quantitative sensory testing including pain pressure thresholds (PPTs) and thermal pressure thresholds was performed at points anatomically local and distant from the hip. RESULTS: Women had significantly greater pain extent (6.71%) than men (2.65%) (z = -2.76, P < 0.01). Across all participants, increased pain extent was significantly associated with higher scores on the Widespread Pain Index (r2  = 0.426, P < 0.05), painDETECT questionnaire (r2  = 0.394, P < 0.05), and Pain Catastrophizing Scale (r2  = 0.413, P < 0.05), and with lower PPTs at the thenar eminence (r2  = -0.410, P < 0.05), vastus lateralis (r2  = -0.530, P < 0.01), vastus medialis (r2  = 0.363, P < 0.05), and greater trochanter (r2  = -0.373, P < 0.05). CONCLUSIONS: Greater pain extent was associated with several measures of signs and symptoms of central sensitization in patients with hip OA. These results support the utility of the pain drawing for identifying signs of central sensitization in patients with hip OA.

[Position paper on medical cannabis and cannabis-based medicines in pain medicine]. / Ein Positionspapier zu medizinischem Cannabis und cannabisbasierten Medikamenten in der Schmerzmedizin.

Since March 2017, the prescription of medical cannabis at the expense of the statutory health insurance is possible after approval by the respective medical services. Chronic pain is the most common indication, as health claims data and the accompanying survey show. From the point of view of the law, a prescription is indicated in cases of serious illness, missing or not indicated established therapeutic approaches and a not entirely remote prospect of improvement of the illness or its symptoms. This describes a broader indication spectrum than can currently be based on randomised controlled clinical trials. There is weak evidence of low efficacy for neuropathic pain. For pain related to spasticity and cancer-related pain there is evidence of improvements in quality of life, but effects on pain are of little relevance. For all other indications, only an individual therapeutic trial can be justified based on the available external evidence. However, this usually corresponds to the demand of "a not entirely remote prospect" of a noticeably positive effect of medical cannabis. It is also problematic that almost no long-term studies for the application and efficacy of flowers and extracts are available.Current knowledge on the use of cannabis-based drugs and, more clearly, medical cannabis for chronic pain is insufficient. The increase in the number of countries with marketing authorisations or exemptions for medicinal cannabis or cannabis-based drugs for chronic pain will also pave the way for larger empirical and population-based studies that will further improve the evidence base of research and clinical use.

[Medicinal cannabis and cannabis-based medication: an appeal to physicians, journalists, health insurances, and politicians for their responsible handling]. / Medizinalcannabis und cannabisbasierte Arzneimittel: ein Appell an Ärzte, Journalisten, Krankenkassen und Politiker für einen verantwortungsvollen Umgang.

Since the adoption of the law of March 6, 2017, any German physician can prescribe medical cannabis flowers and cannabis-based magistral and finished medicinal products. No specific indications for prescriptions are provided in the law. The statutory health insurance companies bear the costs once an application for cost coverage has been approved by the Medical Service of the Health Funds. The German associations of psychiatry (child, adolescents, and adults), neurology, palliative care, addictology, and pain medicine are watching these developments in the media, politics, and medical world with concern due to: the option to prescribe cannabis flowers despite the lack of sound evidence and against the recommendations of the German Medical Association; the lack of distinction between medical cannabis flowers and cannabis-based magistral and finished medical products; the indiscriminately positive reports on the efficacy of cannabis-based medicines for chronic pain and mental disorders; the attempts by the cannabis industry to influence physicians; the increase in potential indications by leaders of medical opinion paid by manufacturers of cannabis-based medicines. The medical associations make the following appeal to journalists: To report on the medical benefits and risks of cannabis-based medicines in a balanced manner. To physicians: to prescribe cannabis-based medicines with caution; to prefer magistral and finished medicinal products over cannabis flowers. To politicians: to consider data according to the standards of evidence-based medicine when making decisions and provide financial support for medical research into cannabis-based medicines.

[Evidence of the efficacy and safety of cannabis medicines for chronic pain management : A methodological minefield]. / Evidenz der Wirksamkeit und Sicherheit von Cannabispräparaten bei chronischen Schmerzen : Ein methodisches Minenfeld.

Recent systematic reviews (SRs) came to divergent conclusions on the efficacy and safety of medical marijuana and cannabis-based medicines for chronic pain management. This paper gives an overview and critical appraisal of the methods of recent SRs of randomized controlled trials (RCTs) with cannabis medicines for chronic pain.Selective search of the literature, incorrect data analyses and presentation in favor of cannabis medicines can be detected in both RCTs and SRs. The more detailed the search of literature (e.g. inclusion of so-called grey literature) and the higher the criteria of the inclusion of studies (such as study duration) and of the clinical relevance of the study findings, the more disappointing are the conclusions of SRs on the efficacy and safety of cannabis medicines. There is moderate quality evidence of a moderate relief of neuropathic pain. Cannabis medicines can be regarded to be third-line therapy for chronic neuropathic pain. There are signals of a lack of efficacy for all other chronic pain syndromes.New high-quality RCTs and approaches, such as network meta-analyses combining different treatments and controlled and observational including additional outcomes than pain relief, are necessary to better define the importance of cannabis medicines for chronic pain management.

Cannabis-based medicines for chronic neuropathic pain in adults.

BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. OBJECTIVES: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. SEARCH METHODS: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. SELECTION CRITERIA: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). AUTHORS' CONCLUSIONS: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

BACKGROUND: Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. METHODS: The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. RESULTS: Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). CONCLUSION: Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype.