No add-on therapeutic benefit of at-home anodal tDCS of the primary motor cortex to mindfulness meditation in patients with fibromyalgia.

OBJECTIVE: This study investigated the efficacy of combining at-home anodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) with mindfulness meditation (MM) in fibromyalgia patients trained in mindfulness. METHODS: Thirty-seven patients were allocated to receive ten daily sessions of MM paired with either anodal or sham tDCS over the primary motor cortex. Primary outcomes were pain intensity and quality of life. Secondary outcomes were psychological impairment, sleep quality, mood, affective pain, mindfulness level, and transcranial magnetic stimulation (TMS) measures of cortical excitability. Outcomes were analyzed pre- and post-treatment, with a one-month follow-up. RESULTS: We found post-tDCS improvement in all clinical outcomes, including mindfulness level, except for positive affect and stress, in both groups without significant difference between active and sham conditions. No significant group*time interaction was found for all clinical and TMS outcomes. CONCLUSIONS: Our findings demonstrate no synergistic or add-on efffect of anodal tDCS of the left M1 compared to the proper effect of MM in patients with fibromyalgia. SIGNIFICANCE: Our findings challenge the potential of combining anodal tDCS of the left M1 and MM in fibromyalgia.

Opioid Use Disorder: A Qualitative Exploratory Analysis of Potential Misunderstandings in Patients with Chronic Non-Cancer Pain.

Purpose: Substance use disorders (SUD) are a challenging comorbidity in patients with chronic non-cancer pain (CNCP) as they complicate diagnosis and therapy, especially when opioids are part of the therapeutic regimen. A definite diagnosis of opioid use disorder (OUD) in patients with CNCP on long-term opioid therapy (LTOT) is a prerequisite for effective and targeted therapy but may be complicated as some criteria of OUD might be attributed to the desire of the patient to relieve the pain. For instance, the desire to increase the dose can be based on both a SUD as well as inadequate pain therapy. Many scientific studies use standardized questions. Therefore, potential misunderstandings due to possible diagnostic overlaps often cannot be clarified. Methods: 14 qualitative guided interviews were conducted and analyzed (Kuckartz content analysis), with the intention to verify if patient's initial response to simple questions based on the wording of the DSM-5, as commonly used in research and practice, were consistent with the results of a more in-depth inquiry. Results: The results suggest that without in-depth investigation, there is a particular risk of false-positive assessment of the DSM-5 criteria for OUD when opioids are prescribed, especially when the questions are considered independently of chronic pain. The risk of a false-negative assessment has also been shown in isolated cases. Conclusion: Only after asking for and describing specific situations it was possible to determine whether the patient's positive or negative answers were based on a misunderstanding of the question. To avoid misdiagnosis, staff conducting DSM-5 interviews should be trained in pain-specific follow-up questions that may help to uncover diagnostic confounding.

[Dealing with "complex" pain patients in eye surgery : Perioperative management of patients with pre-existing chronic pain, opioid consumption and opioid use disorder]. / Umgang mit "komplexen" Schmerzpatienten bei Augeneingriffen : Perioperatives Management von Patienten mit vorbestehenden chronischen Schmerzen, Opioidvormedikation und Opioidabhängigkeit.

The quality of postoperative pain management is still considered insufficient in many cases, also in surgical ophthalmology. Complex constellations and comorbidities, such as pre-existing chronic pain, opioid consumption and opioid use disorders represent a special challenge due to psychosocial influencing factors and sometimes psychological and psychiatric comorbidities but also due to pharmacological effects, such as the development of opioid tolerance, the opioid-induced hyperalgesia. This review article aims to impart knowledge on aspects of these comorbidities and the perioperative management to improve the treatment skills of ophthalmologists in the management of pain in these complex patients.

[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.

Pain reduction in fibromyalgia syndrome through pairing transcranial direct current stimulation and mindfulness meditation: A randomized, double-blinded, sham-controlled pilot clinical trial.

Background: This double-blinded, randomized and sham-controlled pilot clinical trial aimed to investigate the preliminary clinical efficacy and feasibility of combining mindfulness meditation (MM) and transcranial direct current stimulation (tDCS) for pain and associated symptoms in patients with fibromyalgia syndrome (FMS). Methods: Included FMS patients (age: 33 to 70) were randomized to three different groups to receive either ten daily sessions of anodal tDCS over the left primary motor cortex paired with MM for 20 min (active + MM, n = 10), sham tDCS combined with MM (sham + MM, n = 10) or no intervention (NoT, n = 10). Patients in the bimodal therapy groups received a week of training in MM prior to the stimulation. Participants reported pain intensity, the primary outcome, by filling in a pain diary daily throughout the whole study. They were also evaluated for quality of life, pressure pain sensitivity, psychological wellbeing, sleep quality and sleep quantity. Assessments were performed at three time points (baseline, immediately after treatment and one-month follow-up). Results: Participants in the active + MM group did not exhibit reduced pain intensity following the bimodal therapy compared to controls. Patients in active group demonstrated clinically meaningful and significantly higher quality of life following the therapeutic intervention than other groups. There was no significant difference among groups regarding pressure pain sensitivity, sleep parameters and psychological scales. The combined treatment was well tolerated among participants, with no serious adverse effects. Conclusion: This study was the first to pair these two effective non-pharmacological therapies for pain management in FMS. In the light of an underpowered sample size, repetitive anodal tDCS combined with MM did not improve pain or FMS-associated symptoms. However, patients in the active + MM group reported higher quality of life than the control groups. Studies with more participants and longer follow-ups are required to confirm our findings. Clinical trial registration: [www.drks.de], identifier [DRKS00023490].

Patients' self-reported physical and psychological effects of opioid use in chronic noncancer pain-A retrospective cross-sectional analysis.

BACKGROUND: Strong opioids can have unintended effects. Clinical studies of strong opioids mainly report physical side effects, psychiatric or opioid use disorders. To date, too little attention has been paid to the psychological effects of opioids to treat patients with chronic noncancer pain (CNCP). This study aims to identify and measure (i) the nature and frequency of physical and psychological effects and (ii) the degree of physician counseling of patients with CNCP taking strong opioids. METHODS: Within a cross-sectional survey-conducted as part of a randomised controlled online intervention trial (ERONA [Experiencing the risk of overusing opioids among patients with chronic non-cancer pain in ambulatory care])-300 German CNCP patients were surveyed via patient-reported outcome measures regarding on both the side effects from their use of strong opioids as well as their counselling experience. RESULTS: Among the patients' reported effects, the psychological outcomes of the opioids in CNCP were: feeling relaxed (84%), fatigue (76%), dizziness (57%), listlessness (37%), difficulty with mental activities (23%), dulled emotions (17%) and poor memory (17%). Ninety-two per cent of the patients reported having received information about opioid effects, and 46% had discussed cessation of the opioid medication with their physicians before commencing the prescription. CONCLUSIONS: In addition to the well-known physical side effects, patients with CNCP taking strong opioids experience significant psychological effects. In view of these effects, discontinuation of opioid therapy should be discussed early to ensure their benefits do not outweigh their harm. SIGNIFICANCE: In this study, patients with non-cancer pain notice that opioids they have taken do not only cause physical side effects but also may have an impact on their psyche and their emotions and, thus, may also affect quality of life substantially. Clinical trial number: DRKS00020358.

Cannabis-Based Medicines and Medical Cannabis in the Treatment of Nociplastic Pain.

Nociplastic pain is defined as pain due to sensitization of the nervous system, without a sufficient underlying anatomical abnormality to explain the severity of pain. Nociplastic pain may be manifest in various organ systems, is often perceived as being more widespread rather than localized and is commonly associated with central nervous system symptoms of fatigue, difficulties with cognition and sleep, and other somatic symptoms; all features that contribute to considerable suffering. Exemplified by fibromyalgia, nociplastic conditions also include chronic visceral pain, chronic headaches and facial pain, and chronic musculoskeletal pain. It has been theorized that dysfunction of the endocannabinoid system may contribute to persistent pain in these conditions. As traditional treatments for chronic pain in general and nociplastic pain in particular are imperfect, there is a need to identify other treatment options. Cannabis-based medicines and medical cannabis (MC) may hold promise and have been actively promoted by the media and advocacy. The medical community must be knowledgeable of the current evidence in this regard to be able to competently advise patients. This review will briefly explain the understanding of nociplastic pain, examine the evidence for the effect of cannabinoids in these conditions, and provide simplified guidance for healthcare providers who may consider prescribing cannabinoids for these conditions.

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.

Clinical updates on phantom limb pain.

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.

The influence of pain expectation on pain experience after orthopedic surgery: an observational cohort study.

BACKGROUND: Current literature about the effects of patients' expectations on relevant outcome measures is still conflicting and incomplete. The aim of this prospective observational study was to assess the influence of expectations and the fulfillment of expectations on postoperative pain intensity and pain relief. Furthermore, clinical characteristics influencing expectations and the fulfillment of expectations were explored. METHODS: Patients undergoing elective orthopedic surgery were assessed using two standardized self-report questionnaires on the day before surgery and the third postoperative day. One hundred and seventy patients from 21 to 93 years (average age 64.6, SD 14.0 years; 55% female) were consecutively included. RESULTS: While expectations of pain intensity did not correlate with pain experience after surgery, the fulfillment of expectations was associated with postoperative pain experience. Patients whose expectations were fulfilled were found to be more satisfied with the overall treatment as compared to those whose expectations were not fulfilled. Higher levels of expected pain were associated with higher fear of surgery and fear of postoperative pain. Preoperative pain intensity, length of treatment before the surgery, fear of surgery, helplessness and fear of postoperative pain were associated with higher postoperative pain intensity. Lower levels of preoperative fear of surgery and fear of postoperative pain were found to correlate with the fulfillment of pain relief. CONCLUSIONS: Our study indicates that postoperative pain and satisfaction with the treatment are associated with the degree of fulfillment of expectations rather than the expected pain itself.

[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.

[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.

Neck Muscle Stiffness Measured With Shear Wave Elastography in Women With Chronic Nonspecific Neck Pain.

OBJECTIVE: Utilizing shear wave elastography, we compared the stiffness of the neck extensor muscles and the stiffness in muscle-specific regions between women with chronic nonspecific neck pain and asymptomatic controls. DESIGN: Cross-sectional observational study. METHODS: We measured the average muscle stiffness over multiple neck extensor muscles and in regions corresponding approximately to the trapezius, splenius capitis, semispinalis capitis, semispinalis cervicis, and multifidus muscles using ultrasound shear wave elastography in 20 women with chronic nonspecific neck pain and 18 asymptomatic women during multiple tasks. The measurements were automatically quality controlled and computer processed over the complete visible neck region or a large muscle-specific region. RESULTS: Pooled over all tasks, neck muscle stiffness was not significantly different between those with neck pain and asymptomatic controls (neck pain median, 11.6 kPa; interquartile range, 8.9 kPa and control median, 13.3 kPa; interquartile range, 8.6 kPa; P = .175). The measure of neck muscle stiffness was not correlated with the intensity of neck pain or perceived disability. CONCLUSION: Shear wave elastography revealed similar muscle stiffness in people with and without chronic neck pain, despite the sensation of increased neck stiffness in those with chronic neck pain. Therapeutic interventions aiming to reduce neck muscle tone are often based on the assumption that perceived neck stiffness corresponds to objective muscle stiffness. The current results question this assumption. J Orthop Sports Phys Ther 2020;50(4):179-188. Epub 6 Jan 2020. doi:10.2519/jospt.2020.8821.

Opioids for chronic low back pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks of double-blind duration.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non-malignant chronic low back pain. DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 weeks. Studies with a parallel and cross-over design: Based on very low to low-quality evidence, opioids provided no clinically relevant pain relief of 50% or greater, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low-quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross-over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross-over, but not in studies with EERW design. CONCLUSIONS: Opioids may provide a safe and clinically relevant pain relief for 4-15 weeks in highly selected patients. SIGNIFICANCE: Within the context of randomized controlled trials of 4-15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non-malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6-33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo.

Opioids for chronic non-cancer neuropathic pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non-cancer neuropathic pain. DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross-over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo. CONCLUSIONS: Some opioids provided a short-term substantial pain relief in highly selected patients in some neuropathic pain syndromes. SIGNIFICANCE: Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4-12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care.

[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.

Cannabinoids in Pain Management and Palliative Medicine.

BACKGROUND: There are conflicting interpretations of the evidence regarding the efficacy, tolerability, and safety of cannabinoids in pain management and palliative medicine. METHODS: We conducted a systematic review (SR) of systematic reviews of randomized controlled trials (RCT) and prospective long-term observational studies of the use of cannabinoids in pain management and palliative medicine. Pertinent publications from January 2009 to January 2017 were retrieved by a selective search in the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Medline. The methodological quality of the SRs was assessed with the AMSTAR instrument, and the clinical relevance of quantitative data syntheses was assessed according to the standards of the Cochrane Collaboration. RESULTS: Of the 750 publications identified, 11 SRs met the inclusion criteria; 3 of them were of high and 8 of moderate methodological quality. 2 prospective long-term observational studies with medical cannabis and 1 with tetrahydrocannabinol/cannabidiol spray (THC/CBD spray) were also analyzed. There is limited evidence for a benefit of THC/CBD spray in the treatment of neuropathic pain. There is inadequate evidence for any benefit of cannabinoids (dronabinol, nabilone, medical cannabis, or THC/CBD spray) to treat cancer pain, pain of rheumatic or gastrointestinal origin, or anorexia in cancer or AIDS. Treatment with cannabis-based medicines is associated with central nervous and psychiatric side effects. CONCLUSION: The public perception of the efficacy, tolerability, and safety of cannabis-based medicines in pain management and palliative medicine conflicts with the findings of systematic reviews and prospective observational studies conducted according to the standards of evidence-based medicine.

Clinical relevance of persistent postoperative pain after total hip replacement - a prospective observational cohort study.

PURPOSE: The development of persistent postoperative pain may occur following surgery, including total hip replacement. Yet, the prevalence may depend on the definition of persistent pain. This observational cohort study explored whether the prevalence of persistent pain after total hip replacement differs depending on the definition of persistent pain and evaluated the impact of ongoing pain on the patient's quality of life 6 months after surgery. PATIENTS AND METHODS: Pre- and postoperative characteristics of 125 patients undergoing elective total hip replacement were assessed and 104 patients were available for the follow-up interview, 6 months after surgery. RESULTS: Six months after surgery, between 26% and 58% of patients still reported hip pain - depending on the definition of persistent pain. Patients with moderate-to-severe persistent pain intensity (>3 on a numerical rating scale) were more restricted in their daily life activities (Chronic Pain Grade - disability score) but did not differ in reported quality of life (Short-Form 12) from those with no pain or milder pain intensity. Maximal preoperative pain intensity and body mass index were the only independent factors influencing daily function 6 months after total hip replacement. CONCLUSION: These findings support a high prevalence of persistent postoperative pain after total hip replacement and a large variability depending on the definition used. There was a close relation between physical functioning and pain as well as relevance of the patient's psychological state at the time of the operation.

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. PERSPECTIVE: This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials.

Effect of chronic opioid therapy on actual driving performance in non-cancer pain patients.

RATIONALE: Chronic non-cancer pain (CNCP) is a major health problem. Patients are increasingly treated with chronic opioid therapy (COT). Several laboratory studies have demonstrated that long-term use of opioids does not generally impair driving related skills. But there is still a lack of studies investigating on-the-road driving performance in actual traffic. OBJECTIVES: The present study assessed the impact of COT on road-tracking and car-following performance in CNCP patients. METHODS: Twenty CNCP patients, long-term treated with stable doses of opioid analgesics, and 19 healthy controls conducted standardized on-the-road driving tests in normal traffic. Performance of controls with a blood alcohol concentration (BAC) of 0.5 g/L was used as a reference to define clinically relevant changes in driving performance. RESULTS: Standard Deviation of Lateral Position (SDLP), a measure of road-tracking control, was 2.57 cm greater in CNCP patients than in sober controls. This difference failed to reach statistical significance in a superiority test. Equivalence testing indicated that the 95% CI around the mean SDLP change was equivalent to the SDLP change seen in controls with a BAC of 0.5 g/L and did not include zero. When corrected for age differences between groups the 95% CI widened to include both the alcohol reference criterion and zero. No difference was found in car-following performance. CONCLUSIONS: Driving performance of CNCP patients did not significantly differ from that of controls due to large inter-individual variations. Hence in clinical practice determination of fitness to drive of CNCP patients who receive opioid treatments should be based on an individual assessment.