New opioid prescription claims and their clinical indications: results from health administrative data in Quebec, Canada, over 14 years.

OBJECTIVES: Describe new opioid prescription claims, their clinical indications and annual trends among opioid naïve adults covered by the Quebec's public drug insurance plan (QPDIP) for the fiscal years 2006/2007-2019/2020. DESIGN AND SETTING: A retrospective observational study was conducted using data collected between 2006/2007 and 2019/2020 within the Quebec Integrated Chronic Disease Surveillance System, a linkage administrative data. PARTICIPANTS: A cohort of opioid naïve adults and new opioid users was created for each study year (median number=2 263 380 and 168 183, respectively, over study period). INTERVENTION: No. MAIN OUTCOME MEASURE AND ANALYSES: A new opioid prescription was defined as the first opioid prescription claimed by an opioid naïve adult during a given fiscal year. The annual incidence proportion for each year was then calculated and standardised for age. A hierarchical algorithm was built to identify the most likely clinical indication for this prescription. Descriptive and trend analyses were performed. RESULTS: There was a 1.7% decrease of age-standardised annual incidence proportion during the study period, from 7.5% in 2006/2007 to 5.8% in 2019/2020. The decrease was highest after 2016/2017, reaching 5.5% annual percentage change. Median daily dose and days' supply decreased from 27 to 25 morphine milligram equivalent/day and from 5 to 4 days between 2006/2007 and 2019/2020, respectively. Between 2006/2007 and 2019/2020, these prescriptions' most likely clinical indications increased for cancer pain from 34% to 48%, for surgical pain from 31% to 36% and for dental pain from 9% to 11%. Inversely, the musculoskeletal pain decreased from 13% to 2%. There was good consistency between the clinical indications identified by the algorithm and prescriber's specialty or user's characteristics. CONCLUSIONS: New opioid prescription claims (incidence, dose and days' supply) decreased slightly over the last 14 years among QPDIP enrollees, especially after 2016/2017. Non-surgical and non-cancer pain became less common as their clinical indication.

Challenges of acute pain management in older patients.

Adequate management of acute pain in the older population is crucial. However, it is inherently complex because of multiple physiological changes that significantly impact both the pharmacokinetics and pharmacodynamics of medications. Current guidelines promote paracetamol as the first-line analgesic for acute pain in older adults, whereas opioids are advised cautiously for moderate to severe acute pain. However, opioids come with a significant array of side effects, which can be more pronounced in older individuals. Ketamine administered via intranasal (IN) and nebulised inhalation in the emergency department for managing acute pain in older patients shows promising potential for improving pain management and reducing opioid reliance Kampan, Thong-on, Sri-on (2024, Age Ageing, 53, afad255). Nebulised ketamine appears superior in terms of adverse event incidence. However, the adoption of IN or nebulised ketamine in older adult acute pain management remains unclear because of the lack of definitive conclusions and clear guidelines. Nevertheless, these modalities can be valuable options for patients where opioid analgesics are contraindicated or when intravenous morphine titration is impractical or contraindicated. Here, we review these concepts, the latest evidence and propose avenues for research.

Opioids for Acute Musculoskeletal Pain: A Systematic Review with Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of opioids for people with acute musculoskeletal pain against placebo. STUDY DESIGN: Systematic review and meta-analyses of randomised, placebo-controlled trials of opioid analgesics for acute musculoskeletal pain in any setting. The primary outcomes were pain and disability at the immediate timepoint (< 24 h). DATA SOURCES: Multiple databases were searched from their inception to February 22nd, 2023. DATA SYNTHESIS: Continuous outcomes were converted to a 0-100 scale. Dichotomous outcomes were presented as risk differences. Risk of bias and certainty of evidence was assessed. RESULTS: We located 17 trials (1 intravenous and 16 oral route of administration). For adults, high certainty evidence from 11 comparisons shows that oral opioids provide small benefits relative to placebo in the immediate term for pain (mean difference [MD] - 8.8 95% confidence interval [CI] - 12.0 to - 5.6). For disability, the difference is uncertain (MD - 6.2, 95% CI - 17.8 to 5.4). Opioid groups were at higher risk of adverse events (MD 14.3%, 95% CI 8.3-20.4%, very low certainty). There was moderate certainty evidence of a large effect of IV morphine on sciatica pain (MD -42.5, 95% CI - 49.9 to - 35.1, n = 197, 1 study). In paediatric populations, moderate certainty evidence from 3 trials shows that oral opioids probably do not provide benefit beyond that of placebo for pain (MD 6.1, 95% CI - 1.7 to 12.8) and there was no evidence for disability. There was low certainty evidence that there may be no difference in adverse events (MD 10.4%, 95% CI - 0.6 to 21.4%). DISCUSSION: Intravenous morphine likely offers benefits, but oral opioids may not provide clinically meaningful benefits. PROSPERO REGISTRATION: CRD42021249346.

Pain Science in Practice (Part 7): How Is Descending Modulation of Pain Measured?

SYNOPSIS: Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain. This editorial explains how test paradigms, including conditioned pain modulation, offset analgesia, and stress-induced analgesia work, provide an overview of a placebo analgesia circuitry, and discusses how evoking activity in the descending pain modulatory system using specific paradigms can give new insights into how specific treatments work to reduce pain. J Orthop Sports Phys Ther 2024;54(2):1-6. doi:10.2519/jospt.2024.12113.

A non-inferiority randomized controlled trial comparing nebulized ketamine to intravenous morphine for older adults in the emergency department with acute musculoskeletal pain.

OBJECTIVE: Our study aimed to investigate the analgesic efficacy of nebulized ketamine in managing acute moderate-to-severe musculoskeletal pain in older emergency department (ED) patients compared with intravenous (IV) morphine. METHODS: This was a non-inferiority, double-blind, randomized controlled trial conducted at a single medical centre. The patients aged 65 and older, who presented at the ED musculoskeletal pain within 7 days and had a pain score of 5 or more on an 11-point numeric rating scale (NRS), were included in the study. The outcomes were a comparison of the NRS reduction between nebulized ketamine and IV morphine 30 minutes after treatment, incidence of adverse events and rate of rescue therapy. RESULTS: The final study included 92 individuals, divided equally into two groups. At 30 minutes, the difference in mean NRS between the nebulized ketamine and IV morphine groups was insignificant (5.2 versus 5.7). The comparative mean difference in the NRS change from baseline between nebulized ketamine and IV morphine [-1.96 (95% confidence interval-CI: -2.45 to -1.46) and -2.15 (95% CI: -2.64 to -1.66) = 0.2 (95% CI: -0.49 to 0.89)] did not exceed the non-inferiority margin of 1.3. The rate of rescue therapy did not differ between the groups. The morphine group had considerably higher incidence of nausea than the control group (zero patients in the ketamine group versus eight patients (17.4%) in the morphine group; P = 0.006). CONCLUSIONS: Nebulized ketamine has non-inferior analgesic efficacy compared with IV morphine for acute musculoskeletal pain in older persons, with fewer adverse effects.

Effect of Loratadine for Pegfilgrastim-Induced Bone Pain.

AIMS: Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment recommendations include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and/or antihistamine use. However, little research was found comparing these interventions. The study aim was to address the gaps in literature and to explore the use of and perceived effectiveness of loratadine versus acetaminophen or NSAIDs in women with breast cancer treated with pegfilgrastim. This study also sought to understand how patients became aware of loratadine or other treatments for management of bone pain. DESIGN/METHODS: This cross-sectional study used survey methods to collect data from 66 adult female breast cancer patients receiving chemotherapy with pegfilgrastim. RESULTS: The incidence of bone pain was 45% (n = 30) in our sample, but more than half (n = 45; 69%) of the women took either acetaminophen, NSAIDs, or loratadine alone or in combination to prevent bone pain. All medication were rated as effective by patients, with acetaminophen slightly more effective than loratadine, and loratadine more effective than NSAIDs. CONCLUSIONS: Acetaminophen, NSAIDs, and loratadine are easily available and inexpensive. However, unlike acetaminophen and NSAIDs, loratadine is dosed once a day and well tolerated with minimal adverse effects. CLINICAL IMPLICATIONS: Randomized controlled trials are needed to adequately assess the effectiveness of all three medication options. Because little is known about optimal use of any of these medications for pegfilgrastim-induced bone pain, it is also important to identify the optimal time to initiate treatment and ideal treatment duration.

Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine).

BACKGROUND: Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis. METHODS: This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use. RESULTS: 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2-6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3-58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6-52.8%) of their current analgesics. Age (ß = - 0.3, CI - 0.6-0.0), higher pain severity (ß = 0.4, CI 0.1-0.6) and previous cannabis use (ß = 14.7, CI 5.1-24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier. CONCLUSIONS: Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.

Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.

BACKGROUND: Musculoskeletal pain is a condition that affects bones, muscles, and tendons and is present in various diseases and/or clinical conditions. This type of pain represents a growing problem with enormous socioeconomic impacts, highlighting the importance of developing treatments tailored to the patient's needs. TRP is a large family of non-selective cation channels involved in pain perception. Vanilloid (TRPV1 and TRPV4), ankyrin (TRPA1), and melastatin (TRPM8) are involved in physiological functions, including nociception, mediation of neuropeptide release, heat/cold sensing, and mechanical sensation. OBJECTIVE: In this context, we provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models. METHODS: This review describes preclinical models of muscle hyperalgesia induced by intramuscular administration of algogenic substances and/or induction of muscle damage by physical exercise in the masseter, gastrocnemius, and tibial muscles. RESULTS: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. CONCLUSION: Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.

Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.

OBJECTIVE: In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well. PATIENTS AND METHODS: In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS). RESULTS: A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy. CONCLUSIONS: The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.

Topical Chinese patent medicines for chronic musculoskeletal pain: systematic review and trial sequential analysis.

PURPOSE: Chronic musculoskeletal pain (CMP) is defined as persistent or recurrent pain that occurs in the joints, musculo-soft tissue, spine or bones for more than three months and is not completely curable. Although topical Chinese patent medicine (CPM) is the most extensively utilized medication in Asia and is widely used for pain management, its efficacy remains controversial. This article presents a systematic review of clinical studies on the therapeutic properties of topical CPM for CMP patients to better inform clinical decision-making and provide additional and safer treatment options for patients with CMP. METHOD: We performed a comprehensive search on PubMed, Cochrane Library, web of science and Chinese databases (CNKI and WanFang data) from 2010 to 2022. In all the studies, knee osteoarthritis, cervical spondylosis, low back pain, and periarthritis of shoulder met the International Pain Association definition of chronic musculoskeletal pain. We included only randomized controlled trials (RCTs) using topical CPM primarily for chronic musculoskeletal pain in adults. To determine the effect of topical CPM on clinical symptoms, we extracted the Visual Analog Scale (VAS, range 0-10) and the Western Ontario and McMaster Universities Arthritis Index pain scores (WOMAC pain, range 0-20), in which the lower the score, the better the results. We also accepted the comprehensive outcome criteria developed by the Chinese National Institute of Rheumatology as an endpoint (total effectiveness rate, range 0-100%, higher score = better outcome), which assesses the overall pain, physical function and wellness. Finally, trial sequential analysis of VAS pain score and total effectiveness rate was performed using TSA software. RESULTS: Twenty-six randomized controlled trials (n = 3180 participants) compared topical CPM with oral Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (n = 15), topical NSAIDs (n = 9), physiotherapy (n = 5), exercise therapy (n = 4), and intra-articular Sodium hyaluronate injection (n = 2). Sixteen studies found that topical CPM was statistically significant in improving CMP pain (measured by VAS pain and Womac pain scores)(p < 0.05), and 12 studies found topical CPMs to be more clinically effective (assessed by ≥ 30% reduction in symptom severity) in treating patients with CMP (p < 0.05). Trial sequential analysis indicates that the current available evidence is robust, and further studies cannot reverse this result. In most of the studies, randomisation, allocation concealment and blinding were not sufficiently described, and no placebo-controlled trials were identified. CONCLUSION: Most studies showed superior analgesic effects of topical CPM over various control treatments, suggesting that topical CPM may be effective for CMP and is an additional, safe and reasonable treatment option. These reported benefits should be validated in higher-quality RCTs.

Improvement in post-orthodontic chronic musculoskeletal pain after local anesthetic injections in the trigeminal area: a case series.

Orthodontic treatment has been associated with chronic extraoral pain that is often resistant to common treatments such as drugs or physiotherapy, adversely affecting patients' quality of life. In this case series, we discuss the potential impact of orthodontics on chronic cervical spine pain or gonalgia and explore the long-term effect of local anesthetic injections as a possible therapeutic intervention. Six orthodontic patients with chronic cervical spine pain or gonalgia that substantially affected their quality of life were treated with injections of 0.5% procaine into individual lesions and at palpable points of tissue tension in the oral mucosa and extraoral myofascial areas. All patients in this case series reported significant improvement in their chronic pain, with no residual pain recorded at the 6-month follow-up. Injecting local anesthetic at stress points in the oral mucosal and extraoral myofascial regions may be an effective treatment for post-orthodontic neck and knee pain. Further research is required to better understand the potential benefits of this intervention for patients experiencing orthodontic-related musculoskeletal pain.

Factors affecting the intensity of chronic musculoskeletal pain in patients with cardiovascular disease and evaluation of the efficacy of magnesium emulsion cream for muscle cramps.

Chronic musculoskeletal pain (CMP) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to determine the factors associated with the intensity of CMP in patients with underlying CVD and to evaluate the efficacy of Ice Power Magnesium In Strong Cream in patients with muscle cramps. We investigated 396 patients with or without CMP who visited an outpatient cardiology clinic and analyzed the features of CMP and factors associated with pain intensity and specific types of CVD in study 1. We also analyzed 73 patients who had muscle cramps in the lower extremities in study 2 to evaluate the efficacy of Ice Power Magnesium In Strong Cream in reducing pain intensity. In study 1, multivariable linear regression analysis showed that older age (regression coefficient [B] = 0.66, 95% confidence interval [CI], 0.07-1.24), female sex (B = 1.18, 95% CI, 0.59-1.76), presence of hypertension (B = 0.69, 95% CI, 0.05-1.33), and use of calcium supplements (B = 1.27, 95% CI, 0.31-2.24) were significantly associated with a higher intensity of CMP. In study 2, the mean pain scores at baseline, week 2 and week 4 after treatment were 5.99 ± 2.12, 2.92 ± 2.63, and 1.90 ± 2.41, respectively, and the reductions were significant at both week 2 and week 4 after treatment (P < .05). Older age, female sex, hypertension, and use of calcium supplements were associated with an increased intensity of CMP. Ice Power Magnesium In Strong Cream was effective in reducing the pain intensity of muscle cramps in the lower extremities.

Prediction of musculoskeletal pain after the first intravenous zoledronic acid injection in patients with primary osteoporosis: development and evaluation of a new nomogram.

OBJECTIVE: To construct a new prediction nomogram to predict the risk of musculoskeletal pain in patients with primary osteoporosis who receive zoledronic acid intravenously for the first time. METHOD: Clinical data of 368 patients with primary osteoporosis who received the first intravenous injection of zoledronic acid in our hospital from December 2019 to December 2022 were studied. Patients were divided into a musculoskeletal pain group (n = 258) and a non-musculoskeletal pain group (n = 110) based on the presence or absence of musculoskeletal pain 3 days after injection. Statistically significant predictors were screened by logistic regression analysis and the minimum absolute contraction and selection operator (LASSO) to construct a nomogram. The nomogram was evaluated by the receiver operating characteristic (ROC) curve, the calibration curve, the C-index, and the decision curve analysis (DCA) and verified in a validation cohort. RESULTS: The independent predictors of the nomogram were age, serum 25-hydroxyvitamin D, NSAIDs, prior Vitamin D intake, and BMI. The area under the ROC curve (AUC) was 0.980 (95% CI, 0.915-0.987), showing excellent predictive performance. The nomogram c index was 0.980, and the nomogram c index for internal verification remained high at 0.979. Moreover, calibration curves show that the nomogram has good consistency. Finally, the DCA showed that the net benefit of the nomogram was 0.20-0.49. CONCLUSION: Musculoskeletal pain is a common symptom of APR in OP patients treated with intravenous zoledronic acid. Risk factors for musculoskeletal pain after zoledronic acid injection in OP patients were: non-use of NSAIDs, youth (<80 years old), serum 25 (OH) D<30ng /mL, no prior intake of vitamin D, BMI<24 kg /m2. A nomogram constructed from the above predictors can be used to predict musculoskeletal pain after the first zoledronic acid injection.

Continued Opioid Use and Adverse Events Following Provision of Opioids for Musculoskeletal Pain in the Emergency Department: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of continued opioid use or serious adverse events (SAEs) following opioid therapy in the emergency department (ED) for musculoskeletal pain is unclear. The aim of this review was to examine the prevalence of continued opioid use and serious adverse events (SAEs) following the provision of opioids for musculoskeletal pain in the emergency department (ED) or at discharge. METHODS: Records were searched from MEDLINE, EMBASE and CINAHL from inception to 7 October 2022. We included randomised controlled trials and observational studies enrolling adult patients with musculoskeletal pain who were administered and/or prescribed opioids in the ED. Continued opioid use and opioid misuse data after day 4 since ED discharge were extracted. Adverse events were coded using the Common Terminology Criteria for Adverse Events (CTCAE), and those rated as grades 3-4 (severe or life-threatening) and grade 5 (death) were considered SAEs. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Seventy-two studies were included. Among opioid-naïve patients who received an opioid prescription, 6.8-7.0% reported recent opioid use at 3-12 months after discharge, 4.4% filled ≥ 5 opioid prescriptions and 3.1% filled > 90-day supply of opioids within 6 months. The prevalence of SAEs was 0.02% [95% confidence interval (CI) 0, 0.2%] in the ED and 0.1% (95% CI 0, 1.5%) within 2 days. One study observed 42.9% of patients misused opioids within 30 days after discharge. CONCLUSIONS: Around 7% of opioid-naïve patients with musculoskeletal pain receiving opioid therapy continue opioid use at 3-12 months after ED discharge. SAEs following ED administration of an opioid were uncommon; however, studies only monitored patients for 2 days. PROTOCOL REGISTRATION: 10.31219/osf.io/w4z3u.

Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank.

The pharmacological management of musculoskeletal pain starts with NSAIDs, followed by weak or strong opioids until the pain is under control. However, the treatment outcome is usually unsatisfying due to inter-individual differences. To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P = 3.88 × 10-8). Suggestive significant (P < 1 × 10-6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development. Pathway and network analyses identified immunity-related processes and a (putative) central role of EGFR. However, this study should be viewed as a first step to elucidate the genetic background of musculoskeletal pain treatment.

Dexmedetomidine alleviates anxiety-like behaviors in female mice with musculoskeletal pain through SIRT1/p53 axis.

BACKGROUND: Musculoskeletal pain is the most common form of chronic pain. Anxiety increases pain intensity and appears to have a major impact on the prevalence and also disability of musculoskeletal pain in women. We examined the effect of dexmedetomidine (DEX) on anxiety-like behaviors associated with musculoskeletal pain and the underlying molecular mechanism in female mice. METHODS: Musculoskeletal pain was induced by injection of acidified saline into the gastrocnemius muscle in adult female mice, and the von Frey filament test is used to measure mechanical sensitivity. DEX and EX527 (SIRT1 inhibitor) were administered after modelling. Behavioral tests were used for anxiety and motor activity tests. SIRT1, p53 and acetyl-p53 were quantified by Western blot. RESULTS: Adult female mice with musculoskeletal pain exhibit increased fear-like behavior by reducing SIRT1 expression in the medial prefrontal cortex (mPFC). While administration of DEX was able to alleviate mechanical hypersensitivity and anxiety-like behaviors by blocking SIRT1 decline and acetyl-p53 upregulation in mPFC, EX527 inhibited acetyl-p53 rise and reversed the antinociceptive and anxiolytic effects of DEX. CONCLUSION: DEX may alleviate anxiety-like behaviors in mice with musculoskeletal pain via the SIRT1/p53 axis. These results suggest that DEX may have a potential therapeutic role in musculoskeletal pain-induced anxiety.

Prevalence of opioid and nonopioid pain management therapies among Medicare beneficiaries with musculoskeletal pain conditions from 2016 to 2019.

INTRODUCTION: Pain treatment guidelines prioritize nonopioid therapies over opioid medications to prevent opioid-related harms. We examined trends in receipt and intensity of nonpharmacologic, nonopioid medication, and opioid therapies among Medicare beneficiaries. METHODS: Using a 20% national random sample of Medicare data from 2016 to 2019, we identified fee-for-service beneficiaries with ≥2 diagnoses of back, neck, fibromyalgia, or osteoarthritis/joint pain annually. We excluded beneficiaries with cancer. We calculated annual proportions of beneficiaries who received physical therapy (PT), chiropractic care, gabapentin, and opioids, overall and in demographic, geographic, and clinical subgroups. We estimated the intensity of therapies using the annual number of visitsor prescription fills, prescription days' supply, and opioid dose. RESULTS: During 2016-2019, PT receipt increased (22.8% to 25.5%) and the mean number of visits among recipients of PT went from 12 to 13. Chiropractic receipt (~18%) and mean annual visits (~10) remained unchanged. The prevalence of gabapentin receipt was stable at ~22% and the mean annual number of fills was unchanged though gabapentin days increased slightly. Opioid prescribing decreased (56.7% to 46.5%) and reductions in opioid dose and duration were observed. Opioid receipt was high among beneficiaries who were under 65 years, American Indian/Alaska Native, Black/African American, or had opioid use disorder (OUD), in whom nonpharmacologic therapies were also received the least. CONCLUSION: Utilization of nonopioid therapies lagged opioids among Medicare beneficiaries with musculoskeletal pain, with limited changes from 2016 to 2019. As opioid prescribing declines and alternative pain therapy receipt remains low, there are potential increasing risks of pain going untreated or undertreated and individuals seeking illicit opioids to alleviate their pain.

Clin-STAR corner: 2021 update in musculoskeletal pain in older adults with a focus on osteoarthritis-related pain.

Chronic musculoskeletal (MSK) pain remains a leading cause of disability and functional impairment among older adults and is associated with substantial societal and personal costs. Chronic pain is particularly challenging to manage in older adults because of multimorbidity, concerns about treatment-related harm, as well as older adults' beliefs about pain and its management. This narrative review presents data on nine high-quality, peer-reviewed clinical trials published primarily over the past two years that focus on MSK pain management in older adults, of which four were comprehensively reviewed. These studies address contributors to knee osteoarthritis (OA) pain (insomnia), provide evidence for digital delivery or artificial intelligence driven behavioral interventions and potentially more efficient/equally effective modes of delivering glucocorticoids for OA; each of the selected studies have potential for scalability and meaningful impact in the care of older adults.

Efficacy and safety of duloxetine in chronic musculoskeletal pain: a systematic review and meta-analysis.

BACKGROUND: Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor in the treatment of CMP. Duloxetine is an effective treatment option for patients with CMP as its antidepressant effect. The purpose of this article is to evaluate the efficacy and safety of duloxetine in treating CMP. DATABASES AND DATA TREATMENT: We searched PubMed, Web of Science, Embase, Cochrane Library from inception to May, 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of duloxetine versus placebo in patients with CMP were included. We identified 13 articles and studied a population of 4201 participants in 4 countries. RESULTS: This meta-analysis showed that the duloxetine has statistically significant compared with the placebo control, benefits on 24-hour average pain, living quality, physical function, and global impressions and there was no difference in the incidence of serious adverse event. In general, duloxetine can improve mood and pain level at the same time. CONCLUSIONS: This review shows a significant contribution of duloxetine to CMP symptom relief. This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression, and has no obvious serious adverse reactions. However, additional studies are required to confirm the relationship between psychological diseases and chronic pain and explore their internal links.