Efficacy of interventions targeted at physician prescribers of opioids for chronic non-cancer pain: an overview of systematic reviews.

BACKGROUND: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour. METHODS: We searched MEDLINE, Embase, and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews; and Epistemonikos. We included systematic reviews that evaluate any type of intervention aimed at impacting opioid prescriber behaviour for adult CNCP in an outpatient setting. RESULTS: We identified three full texts for our review that contained 68 unique primary studies. The main interventions we evaluated were structured prescriber education (one review) and prescription drug monitoring programmes (PDMPs) (two reviews). Due to the paucity of data available, we could not determine with certainty that education interventions improved outcomes in deprescribing. There is some evidence that PDMPs decrease the number of adverse opioid-related events, increase communication among healthcare workers and patients, modify healthcare practitioners' approach towards their opioid prescribed patients, and offer more chances for education and counselling. CONCLUSIONS: Our overview explores the possibility of PDMPs as an opioid deprescribing intervention and highlights the need for more high-quality primary research on this topic.

Trajectories of opioid consumption as predictors of patient-reported outcomes among individuals attending multidisciplinary pain treatment clinics.

PURPOSE: This study aimed to identify opioid consumption trajectories among persons living with chronic pain (CP) and put them in relation to patient-reported outcomes 6 months after initiating multidisciplinary pain treatment. METHODS: This study used data from the Quebec Pain Registry (2008-2014) linked to longitudinal Quebec health insurance databases. We included adults diagnosed with CP and covered by the Quebec public prescription drug insurance plan. The daily cumulative opioid doses in the first 6 months after initiating multidisciplinary pain treatment were transformed into morphine milligram equivalents. An individual-centered approach involving principal factor and cluster analyses applied to longitudinal statistical indicators of opioid use was conducted to classify trajectories. Multivariate regression models were applied to evaluate the associations between trajectory group membership and outcomes at 6-month follow-up (pain intensity, pain interference, depression, and physical and mental health-related quality of life). RESULTS: We identified three trajectories of opioid consumption: "no or very low and stable" opioid consumption (n = 2067, 96.3%), "increasing" opioid consumption (n = 40, 1.9%), and "decreasing" opioid consumption (n = 39, 1.8%). Patients in the "no or very low and stable" trajectory were less likely to be current smokers, experience polypharmacy, use opioids or benzodiazepine preceding their first visit, or experience pain interference at treatment initiation. Patients in the "increasing" opioid consumption group had significantly greater depression scores at 6-month compared to patients in the "no or very low and stable" trajectory group. CONCLUSION: Opioid consumption trajectories do not seem to be important determinants of most PROs 6 months after initiating multidisciplinary pain treatment.

The current state of knowledge on care for co-occurring chronic pain and opioid use disorder: A scoping review.

BACKGROUND AND AIMS: Opioid use disorder often co-occurs with chronic pain but assessment and treatment of these co-occurring disorders is complex. This review aims to identify current treatments and delivery models for co-occurring chronic pain and opioid use disorder (OUD) documented in the scientific literature. DESIGN: Scoping review. METHODS: The review was conducted in six databases in June 2022 (no time limit): CINAHL, PsycINFO, Web of Science, Cochrane, PubMed and Embase. The PRISMA-ScR checklist was used to guide reporting. RESULTS: Forty-seven publications addressing the issue of co-occurring chronic pain and OUD management were included. Randomized controlled trials provide evidence for the effectiveness of opioid agonist treatments (OAT) such as methadone or buprenorphine/naloxone, as well as for combining OAT with Mindfulness-Oriented Recovery Enhancement or cognitive behavioural therapy. A number of other pharmacological treatments (opioid and nonopioid), nonpharmacological treatments (e.g. physiotherapy) and service delivery models (e.g. simultaneous treatment of comorbidities, interdisciplinary and interprofessional collaboration) are also underlined. In most cases, authors recommend a combination of strategies to meet patient needs. CONCLUSIONS: The scoping review reveals gaps in evidence-based knowledge to effectively care for co-occurring chronic pain and OUD, but several experts recommend the uptake of known 'best' practices such as integrated treatment of the multiple biopsychosocial dimensions of the co-occurring disorders as well as collaborative interdisciplinary work. CLINICAL RELEVANCE: Improving services is dependent on alleviating barriers such as working in silos, the costs associated with nonpharmacological treatments, and the double stigma associated with pain in people with a substance use disorder.

One session of repetitive transcranial magnetic stimulation induces mild and transient analgesic effects among female individuals with painful temporomandibular disorders.

OBJECTIVE: Temporomandibular disorders (TMD) are characterised by chronic pain and dysfunction in the jaw joint and masticatory muscles. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential non-invasive treatment for chronic pain; however, its effectiveness in individuals with TMD has not been thoroughly investigated. This study aimed to evaluate the immediate and sustained (over seven consecutive days) effects of a single session of active rTMS compared to sham stimulation on pain intensity and pain unpleasantness in individuals with TMD. METHODS: A randomised, double-blind, sham-controlled trial enrolled 41 female participants with chronic TMD. Pain intensity and pain unpleasantness were assessed immediately pre- and post-intervention, as well as twice daily for 21 days using electronic diaries. Secondary outcomes included pain interference, sleep quality, positive and negative affect and pain catastrophizing. Adverse effects were monitored. Repeated measures ANOVA and multilevel modelling regression analyses were employed for data analysis. RESULT: Active rTMS demonstrated a significant immediate mild reduction in pain intensity and pain unpleasantness compared to sham stimulation. However, these effects were not sustained over the 7-day post-intervention period. No significant differences were observed between interventions for pain interference, sleep quality and negative affect. A minority of participants reported minor and transient side effects, including headaches and fatigue. CONCLUSION: A single session of active rTMS was safe and led to immediate mild analgesic effects in individuals with TMD compared to sham stimulation. However, no significant differences were observed between interventions over the 7-day post-intervention period. Based on this study, rTMS stimulation appears to be a promising safe approach to be tested in TMD patients with longer stimulation protocols.

French-Canadian Translation and Cultural Adaptation of the Clinical Opiate Withdrawal Scale: The COWS-FC.

OBJECTIVE: The main objective of the present study was to develop a French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) for the assessment of opioid withdrawal symptoms in clinical and research settings. METHODS: The French-Canadian translation and cultural adaptation of the COWS was performed following guidelines for the translation and cross-cultural adaptation of self-report measures. The steps consisted of (1) initial translation from English to French, (2) synthesis of the translation, (3) back-translation from French to English, (4) expert committee meeting, (5) test of the prefinal version among healthcare professionals and (6) review of final version by the expert committee. The expert committee considered four major areas where the French-Canadian version should achieve equivalence with the original English-version of the COWS. These areas were (1) semantic equivalence; (2) idiomatic equivalence; (3) experiential equivalence and (4) conceptual equivalence. RESULTS: Rigorous steps based on the guidelines for the translation and cultural adaptation of assessment tools were followed, which led to a semantically equivalent version of the COWS. After a pretest among healthcare professionals, members from the expert committee agreed upon slight modifications to the French-Canadian version of the COWS to yield a final COWS-FC version. CONCLUSIONS: A French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) was developed. The COWS-FC could be used for the assessment of opioid withdrawal symptoms in clinical and research settings.

Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors. METHODS: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity. RESULTS: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related "positive" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain. CONCLUSIONS: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories.

The Effect of Overdose Education and Naloxone Distribution: An Umbrella Review of Systematic Reviews.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author's Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

The Effect of Overdose Education and Naloxone Distribution: An Umbrella Review of Systematic Reviews.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author's Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

Anxiety and Fear Avoidance Beliefs and Behavior May Be Significant Risk Factors for Chronic Opioid Analgesic Therapy Reliance for Patients with Chronic Pain-Results from a Preliminary Study.

OBJECTIVE: To describe differences between patients with chronic, non-cancer pain (CNCP) who were successfully able to cease full mu agonist chronic opioid analgesic therapy (COAT), and those who exhibited refractory COAT reliance, among those who participated in a multidisciplinary program designed for COAT cessation. DESIGN: A retrospective review of electronic medical records (EMR) data was organized for preliminary analysis. SETTING: A multicenter private practice specializing in CNCP, which received patient referrals from the surrounding geographical area of primary and specialty care offices in Northern California. SUBJECTS: Data from 109 patients with CNCP who participated in a multidisciplinary program to cease COAT between the dates of October 2017 to December 2019 were examined. METHODS: EMR data, pre-COAT cessation, of oral morphine milligram equivalence (MME) and validated questionnaire responses assessing anxiety and fear-based beliefs and behavior, as well as opioid misuse, were extracted and compared between those who successfully ceased COAT and those who did not. RESULTS: Patients who were unsuccessful at COAT cessation reported significantly higher Fear Avoidance Beliefs Questionnaire (FAB) scores. No significant differences were found based on incoming MME amounts, Current Opioid Misuse Measure (COMM) or Tampa Scale of Kinesiophobia (TSK) scores. Pain Catastrophizing Scale (PCS) scores showed a split pattern with unclear significance. CONCLUSIONS: Results suggest that fear avoidance beliefs and behavior, as measured by the FAB, play a significant role in refractory COAT reliance for patients with CNCP.

Sleep and pain: recent insights, mechanisms, and future directions in the investigation of this relationship.

Sleep disturbances and chronic pain are considered public health concerns. They are frequently associated, and the direction of its relationship and possible mechanisms underlying it are frequently debated. The exploration of the sleep-pain association is of great clinical interest to explore in order to steer potential therapeutic avenues, accommodate the patient's experience, and adapt the common practice of health professionals. In this review, the direction between sleep-pain in adult and pediatric populations will be discussed. Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored. Finally, directions for future studies on this area will be discussed, opening up to the addition of tools such as brain imaging (e.g., fMRI), electrophysiology and non-invasive brain stimulation techniques. Such resources paired with artificial intelligence are key to personalized medicine management for patients facing pain and sleep interacting conditions.

Dental sleep medicine: Time to incorporate sleep apnoea education in the dental curriculum.

Dental sleep medicine is a discipline that includes conditions such as sleep breathing disorders (eg snoring and sleep apnoea), sleep bruxism, orofacial pain and sleep-related complaints, and to some extent gastro-oesophageal reflux disorder and/or insomnia. Obstructive sleep apnoea (OSA) is a life-threatening condition that dentists need to identify and manage when indicated in order to increase patient well-being and to be taken in consideration in the dental curriculum. The main objective of this paper is to highlight the relevance of dental sleep medicine in the context of dental education, and to discuss potential educational content for integration in the dental curriculum with a focus on OSA, a condition that is not yet integrated in many dental training curricula around the world.

The Association Between Daily Physical Activity and Pain Among Patients with Knee Osteoarthritis: The Moderating Role of Pain Catastrophizing.

OBJECTIVE: The primary objective of this study was to examine the day-to-day association between physical activity and pain intensity among a sample of patients with knee osteoarthritis (KOA) and the potential moderation of this association by negative cognitive processes. METHODS: In this micro-longitudinal daily diary study, KOA patients (N = 121) completed questionnaires assessing pain (Brief Pain Inventory) and psychosocial functioning (pain catrophizing scale, WOMAC McMaster Universities Osteoarthritis Index function, Patient-Reported Outcomes Measurement Information System [PROMIS; anxiety and depression], the Godin-Shephard Leisure-Time Physical Activity questionnaire, the six-minute walking test) and were then asked to report their levels of physical activity and pain intensity once per day for a period of seven days using an electronic diary. RESULTS: Multilevel modeling analyses indicated that day-to-day increases in physical activity were associated with heightened levels of pain intensity (B = 0.13 SE = 0.03, P < 0.001). In addition, it was revealed that the association between physical activity and pain intensity was moderated by catastrophizing (B = -0.01 SE = 0.002, P < 0.05), with patients scoring higher in catastrophizing showing a relatively stronger link between day-to-day physical activity and increased knee pain. This effect was specific to catastrophizing, as depression and anxiety did not moderate the activity-pain relationship (P > 0.05). CONCLUSIONS: Our findings suggest that increases in daily physical activity are associated with concurrent increases in KOA patients' levels of knee pain, particularly among patients reporting higher levels of pain catastrophizing. These results may have clinical implications for the design and testing of interventions targeted at reducing catastrophizing and increasing physical activity among patients with chronic osteoarthritis pain.

Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis.

BACKGROUND: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. METHOD: Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. RESULTS: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). CONCLUSIONS: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT01383954 . Registered June 22, 2011.

Distraction analgesia in chronic pain patients: the impact of catastrophizing.

BACKGROUND: Diverting attention away from noxious stimulation (i.e., distraction) is a common pain-coping strategy. Its effects are variable across individuals, however, and the authors hypothesized that chronic pain patients who reported higher levels of pain catastrophizing would derive less pain-reducing benefit from distraction. METHODS: Chronic pain patients (n=149) underwent psychometric and quantitative sensory testing, including assessment of the temporal summation of pain in the presence and absence of a distracting motor task. RESULTS: A simple distraction task decreased temporal summation of pain overall, but, surprisingly, a greater distraction analgesia was observed in high catastrophizers. This enhanced distraction analgesia in high catastrophizers was not altered when controlling for current pain scores, depression, anxiety, or opioid use (analysis of covariance [ANCOVA]: F=8.7, P<0.005). Interestingly, the magnitude of distraction analgesia was inversely correlated with conditioned pain modulation (Pearson R=-0.23, P=0.005). CONCLUSION: Distraction produced greater analgesia among chronic pain patients with higher catastrophizing, suggesting that catastrophizing's pain-amplifying effects may be due in part to greater attention to pain, and these patients may benefit from distraction-based pain management approaches. Furthermore, these data suggest that distraction analgesia and conditioned pain modulation may involve separate underlying mechanisms.

The association between catastrophizing and craving in patients with chronic pain prescribed opioid therapy: a preliminary analysis.

BACKGROUND: A growing number of studies have shown that opioid craving (i.e., the perceived need or desire to consume opioids) is one of the strongest determinants of prescription opioid misuse in patients with chronic pain prescribed opioid therapy. To date, however, the factors that are associated with craving in patients with pain remain largely unexplored. Based on previous research, there is reason to believe that catastrophizing might be associated with heightened opioid craving. OBJECTIVES: To test the hypothesis that catastrophizing would be associated with heightened craving in patients with chronic pain prescribed long-term opioid therapy. DESIGN AND SUBJECTS, AND METHODS: In this cross-sectional study, 109 patients with chronic pain were asked to provide self-reports of catastrophizing and craving. Patients also provided self-reports of pain intensity and depressive symptoms. RESULTS: We found that higher levels of catastrophizing were associated with higher levels of craving. Importantly, results of a regression analysis revealed that the association between catastrophizing and craving remained significant even after controlling for a host of demographic (i.e., age, sex), psychological (i.e., depressive symptoms), medical (i.e., pain intensity, pain duration), and medication regimen (i.e., opioid doses) variables. CONCLUSIONS: Our preliminary findings provide valuable new insights into the determinants of craving in patients with pain. The finding that catastrophizing was associated with craving even after controlling for a host of demographic, psychological, medical, and medication regimen variables is particularly striking, and raises questions concerning the factors that underlie the association between catastrophizing and craving in patients prescribed opioid therapy.

The Impact of Sleep Disturbances on Endogenous Pain Modulation: A Systematic Review and Meta-Analysis.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVE: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

A Descriptive Analysis of Adverse Event Reports from the Quebec Cannabis Registry.

INTRODUCTION: Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation. METHODS: The Quebec Cannabis Registry (QCR) was a prospective registry of adults enrolled through participating physicians when they initiated MC between May 2015 and October 2018. Follow-up ended at MC discontinuation, loss to follow-up, three years, or end of data collection (May 2019). Data were collected at baseline and at follow-up visits every three months for the first two years, then once in the third year. Physicians filled adverse event (AE) reports, which were coded using MedDRA® preferred terms (PTs), and descriptive analyses were conducted. RESULTS: A total of 2991 patients were enrolled (mean age 50.9 years, 50.2% females). During follow-up, 108 patients (3.6%) experienced moderate or severe AEs, yielding 111 AE reports (three patients had two reports) and 214 AEs (average 1.9 AEs per report). Mild AEs were recorded as a reason for MC discontinuation for nine patients, but no AE reports were available. The most common PTs for ingested MC (62 reports) were dizziness (12.9%), nausea (11.3%), somnolence (9.7%), and vomiting (8.1%), and for inhaled MC (23 reports), headache (13.0%) was the most common. The most frequent PTs associated with tetrahydrocannabinol (THC)-dominant MC (25 reports) were dizziness and somnolence (12.0% each); for cannabidiol (CBD)-dominant MC (20 reports), vomiting (20.0%) was most common; and dizziness (17.2%), nausea (13.8%), somnolence (10.3%), and headache (8.6%) were the most frequent for balanced MC (58 reports). CONCLUSION: No new safety concerns were identified relative to the published literature, although notable differences in AE profile between modes of administration and cannabinoid content ratios should be considered by health professionals. Further work identifying and managing risk factors for AEs is warranted to maintain a favorable benefit-risk balance for MC.

The Contribution of Sleep Quality and Psychological Factors to the Experience of Within-Day Pain Fluctuations Among Individuals With Temporomandibular Disorders.

We assessed the impact of day-to-day sleep quality and psychological variables (catastrophizing, negative affect, and positive affect) to within-day pain fluctuations in 42 females with painful temporomandibular disorders (TMD) using electronic diaries. More specifically, we examined the contribution of these variables to the likelihood of experiencing pain exacerbations defined as 1) an increase of 20 points (or more) in pain intensity on a 0 to 100 visual analog scale from morning to evening, and/or 2) a transition from mild-to-moderate pain over the course of the day; and pain decreases defined as 3) a decrease of 20 points (or more) in pain intensity (visual analog scale) from morning to evening, and/or 4) a reduction from moderate-to-mild pain over the day. The results indicated significantly main effects of sleep on both pain exacerbation outcomes (both P's < .05), indicating that nights with better sleep quality were less likely to be followed by clinically meaningful pain exacerbations on the next day. The results also indicated that days characterized by higher levels of catastrophizing were associated with a greater likelihood of pain exacerbations on the same day (both P's < .05). Daily catastrophizing was the only variable significantly associated with within-day pain decrease indices (both P's < .05). None of the other variables were associated with these outcomes (all P's > .05). These results underscore the importance of addressing patients' sleep quality and psychological states in the management of painful TMD. PERSPECTIVES: These findings highlight the significance of sleep quality and pain catastrophizing in the experience of within-day pain fluctuations among individuals with TMD. Addressing these components through tailored interventions may help to alleviate the impact of pain fluctuations and enhance the overall well-being of TMD patients.

Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.

OBJECTIVES: To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. DESIGN, SUBJECTS, AND METHODS: In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). RESULTS: Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). CONCLUSIONS: Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function.