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Long-Term Use of Muscle Relaxant Medications for Chronic Pain: A Systematic Review

Author/s: 
Benjamin J Oldfield, Brynna Gleeson, Kenneth L Morford, Zoe Adams, Melissa C Funaro, William C Becker, Jessica S Merlin

Importance: Stricter opioid prescribing guidelines have increased prescriptions of skeletal muscle relaxants (SMRs) for chronic pain, but the efficacy of long-term use of SMRs for chronic pain is unknown.

Objective: To systematically review the effectiveness or efficacy of long-term use of SMRs for chronic pain.

Evidence review: Two reviewers systematically searched Ovid MEDLINE, Embase (Ovid), Web of Science, CINAHL, and Cochrane through December 4, 2023. They included articles published in English, Spanish, or Italian. Only randomized clinical trials (RCTs) and cohort studies with comparator groups evaluating at least 1-month duration of SMRs for chronic pain were included. The reviewers dually reviewed data abstraction, risk-of-bias, and quality. They characterized studies by chronic pain syndrome: low back pain, fibromyalgia, headaches, painful cramps or spasticity, and other syndromes.

Findings: A total of 30 RCTs with 1314 participants and 14 cohort studies with 1168 participants assessed SMRs for chronic pain. Studies were primarily short-term (4-6 weeks). Nine unique SMRs were represented by the studies identified. Eleven studies (25%) examined baclofen, 8 (18%) examined tizanidine, and 7 (16%) examined cyclobenzaprine. Evidence for effectiveness was strongest for SMRs used for trigeminal neuralgia, neck pain, and painful cramps; evidence suggested SMRs for fibromyalgia, low back pain, and other syndromes were not more beneficial than placebo. The most common adverse effects were sedation and dry mouth. RCTs had a low to moderate risk of bias, and the quality of cohort studies was fair to good.

Conclusions and relevance: In this systematic review of long-term use of SMRs for chronic pain, findings suggest that their long-term use may benefit patients with painful spasms or cramps and neck pain; their long-term use for low back pain, fibromyalgia, and headaches did not appear to be beneficial. Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.

Keywords 
chronic pain muscle relaxants

Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress

Author/s: 
Shi, Yu, Wu, Wen

Chronic pain conditions impose significant burdens worldwide. Pharmacological treatments like opioids have limitations. Non-invasive non-pharmacological therapies (NINPT) encompass diverse interventions including physical, psychological, complementary and alternative approaches, and other innovative techniques that provide analgesic options for chronic pain without medications.
Main body

This review elucidates the mechanisms of major NINPT modalities and synthesizes evidence for their clinical potential across chronic pain populations. NINPT leverages peripheral, spinal, and supraspinal mechanisms to restore normal pain processing and limit central sensitization. However, heterogeneity in treatment protocols and individual responses warrants optimization through precision medicine approaches.
Conclusion

Future adoption of NINPT requires addressing limitations in standardization and accessibility as well as synergistic combination with emerging therapies. Overall, this review highlights the promise of NINPT as a valuable complementary option ready for integration into contemporary pain medicine paradigms to improve patient care and outcomes.

Keywords 
chronic pain

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

Author/s: 
Owoicho Adogwa, M. Cary Reid, Sai Chilakapati, Una E. Makris

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.

Keywords 
aging back pain osteoarthritis chronic pain comorbid conditions

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Author/s: 
McDonagh, M. S., Wagner, J., Ahmed, A. Y., Fu, R., Morasco, B., Kansagara, D., Chou, R.

In an effort to address the opioid epidemic, a prominent goal of current research is to identify alternative treatments with equal or better benefits for pain while avoiding potential unintended consequences that could result in harms.

This 'living' systematic review assesses the effectiveness and harms of cannabis and other plant-based treatments for chronic pain conditions. For the purposes of this review, plant-based compounds (PBCs) included are those that are similar to opioids in effect and that have the potential for addiction, misuse, and serious adverse effects; other PBCs such as herbal treatments are not included. The intended audience includes policy and decision makers, funders and researchers of treatments for chronic pain, and clinicians who treat chronic pain.

The report will be updated on a quarterly basis.

Keywords 
Policy Goals chronic pain cannabis use opiod misuse

Chronic anal pain: A review of causes, diagnosis, and treatment

Author/s: 
Knowles, C. H., Cohen, R. C.

Chronic anal pain is diffi cult to diagnose and treat, especially with no obvious anorectal cause apparent on clinical examination. This review identifi es 3 main diagnostic
categories for chronic anal pain: local causes, functional
anorectal pain, and neuropathic pain syndromes. Conditions covered within these categories include proctalgia
fugax, levator ani syndrome, pudendal neuralgia, and coccygodynia. The signs, symptoms, relevant diagnostic tests,
and main treatments for each condition are reviewed.

Keywords 
Anal Pain Causes diagnosis treatment chronic pain

Evaluation of a Chronic Pain Screening Program Implemented in Primary Care

Author/s: 
Bifulco, L., Anderson, D. R., Blankson, M. L, Channamsetty, V., Blaz, J. W., Nguyen-Louie, T., Scholle, S. H.

Importance: Although pain is among the most common symptoms reported by patients, primary care practitioners (PCPs) face substantial challenges identifying and assessing pain.

Objective: To evaluate a 2-step process for chronic pain screening and follow-up in primary care.

Design, setting, and participants: A cross-sectional study of patients with a primary care visit between July 2, 2018, and June 1, 2019, was conducted at a statewide, multisite federally qualified health center. Participants included 68 PCPs and 58 medical assistants from 13 sites who implemented the screening process in primary care, and 38 866 patients aged 18 years or older with a primary care visit during that time.

Exposures: Single-question assessment of pain frequency, followed by a 3-question PEG (pain, enjoyment of life, general activity) functional assessment for patients with chronic pain.

Main outcomes and measures: Adherence to a 2-step chronic pain screening and PEG process, proportion of patients with positive screening results, mean PEG pain severity greater than or equal to 7, and documented chronic painful condition diagnosis in patient's electronic health record between 1 year before and 90 days after screening.

Results: Of 38 866 patients with a primary care visit, 31 600 patients (81.3%) underwent screening. Mean (SD) age was 46.2 (15.4) years, and most were aged 35 to 54 years (12 987 [41.1%]), female (18 436 [58.3%]), Hispanic (14 809 [46.9%]), and English-speaking (22 519 [71.3%]), and had Medicaid insurance (18 442 [58.4%]). A total of 10 262 participants (32.5%) screened positive and, of these, 9701 (94.5%) completed the PEG questionnaire. PEG responses indicated severe pain interference with activities of daily living (PEG ≥7) in 5735 (59.1%) participants. A chronic painful condition had not been diagnosed in 4257 (43.9%) patients in the year before screening. A new chronic painful condition was diagnosed at screening or within 90 days in 2250 (52.9%) patients. Care teams found the workflow acceptable, but cited lengthy administration time, challenges with comprehension of the PEG questions, and limited comprehensiveness as implementation barriers.

Conclusions and relevance: A systematic, 2-step process for chronic pain screening and functional assessment in primary care appeared to identify patients with previously undocumented chronic pain and was feasible to implement. Patient-provided information on the frequency of pain, pain level, and pain interference can help improve the assessment and monitoring of pain in primary care.

Keywords 
chronic pain Screening Program primary care Pain Measurement

Challenges and Approaches to Population Management of Long-Term Opioid Therapy Patients

Author/s: 
Stephens, Kari A., Ike, Brooke, Baldwin, Laura-Mae, Packer, Christine, Parchman, Michael

Purpose: Primary care is challenged with safely prescribing opioids for patients with chronic noncancer pain (CNCP), specifically to address risks for overdose, opioid use disorder, and death. We identify sociotechnical challenges, approaches, and recommendations in primary care to effectively track and monitor patients on long-term opioid therapy, a key component for supporting adoption of opioid prescribing guidelines.

Methods: We examined qualitative data (field notes and postintervention interview and focus group transcripts) from 6 rural and rural-serving primary care organizations with 20 clinic locations enrolled in a study evaluating a practice redesign program to improve opioid medication management for CNCP patients. Two independent researchers used content analysis to categorize data into key themes to develop an understanding of sociotechnical factors critical to creating and implementing an approach to tracking and monitoring of patients on long-term opioid therapy in primary care practices.

Results: Four factors were critical to developing a tracking and monitoring system. For each we describe common challenges and approaches used by the clinics to overcome then. The first factor, buy-in and participation, was essential for accomplishing the other 3. The other factors occurred sequentially: 1) cohort identification-finding the right patients, 2) data collection and extraction-tracking the right data, and 3) data use-monitoring patients and adjusting care processes.

Conclusions: We identified common challenges and approaches to tracking and monitoring patients using long-term opioid therapy for CNCP in primary care. Based on these findings we provide recommendations to build capacity for tracking and monitoring for organizations that are engaged in improving safe opioid-prescribing practices for CNCP in primary care.

Keywords 
Capacity Building Chronic Disease chronic pain Disease Management Drug Overdose 2019-nCOV 1,4-DMAA primary health care RISEOK

AAFP Chronic Pain Management Toolkit

Chronic pain is common in the U.S., with anywhere from 11% to 40% of the adult population reporting daily pain.1 Approximately one-third of patients experiencing pain receive a pain medication.2 While the number of prescriptions for pain management have declined in recent years3, opioid misuse remains a significant public health crisis. Roughly 21-29% of patients who are prescribed opioids for chronic pain will misuse them.4

This increase leads to a rise in opioid overdoses—at least half are attributed to prescription medications—and morbidity and mortality. Numerous groups—including the AAFP, other medical societies, the National Academy of Medicine and the U.S. Congress—are emphasizing the need to improve chronic pain care.

Keywords 
RISEOK opioids chronic pain pain management Opiate Overdose

Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review Update. Comparative Effectiveness Review No. 227

Author/s: 
Skelly, AC, Chou, R, Dettori, JR, Turner, JA, Friedly, JL, Rundell, SD, Fu, Brodt, ED, Wasson, N, Kantner, S, Ferguson, AJR

Objectives. We updated the evidence from our 2018 report assessing persistent improvement in outcomes following completion of therapy for noninvasive nonpharmacological treatment for selected chronic pain conditions.

Data sources. Electronic databases (Ovid MEDLINE®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews) through November 2017 (for prior report) and from September 2017 through September 2019 (for this update report), reference lists, ClinicalTrials.gov, and our previous report.

Review methods. Using predefined criteria, we selected randomized controlled trials (RCTs) of noninvasive nonpharmacological treatments for five common chronic pain conditions (chronic low back pain; chronic neck pain; osteoarthritis of the knee, hip, or hand; fibromyalgia; and tension headache) that reported results for a at least 1 month postintervention. We analyzed effects and assessed strength of evidence (SOE) at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months).

Results. We included 233 RCTs (31 new to this update). Many were small (N<70), and evidence beyond 12 months after treatment completion was sparse. The most common comparison was with usual care. Evidence on harms was limited, with no evidence suggesting increased risk for serious treatment-related harms for any intervention. Effect sizes were generally small for function and pain.

Chronic low back pain: Psychological therapies were associated with small improvements compared with usual care or an attention control for both function and pain at short-term, intermediate-term, and long-term followup (SOE: moderate). Function improved over short and/or intermediate term for exercise, low-level laser therapy, spinal manipulation, massage, yoga, acupuncture, and multidisciplinary rehabilitation (SOE moderate at short term for exercise, massage, and yoga; low for all others). Improvements in pain at short term were seen for massage, mindfulness-based stress reduction, acupuncture, and multidisciplinary rehabilitation (SOE: moderate), and exercise, low-level laser therapy, and yoga (SOE: low). At intermediate term, spinal manipulation, yoga, multidisciplinary rehabilitation (SOE: moderate) and exercise and mindfulness-based stress reduction (SOE: low) were associated with improved pain. Compared with exercise, multidisciplinary rehabilitation improved both function and pain at short and intermediate terms (small effects, SOE: moderate.)

Chronic neck pain: In the short term, low-level laser therapy (SOE: moderate) and massage (SOE: low) improved function and pain. Exercise in general improved function long term, and combination exercise improved function and pain both short and long term compared with usual care (SOE: low). Acupuncture improved function short and intermediate term, but there was no pain improvement compared with sham acupuncture (SOE: low). Compared with acetaminophen, Pilates improved both function and pain (SOE: low).

Osteoarthritis pain: Exercise resulted in small improvements in function and pain at short-term (SOE: moderate) and long-term (SOE: low), and moderate improvement at intermediate-term (SOE: low) followup for knee osteoarthritis versus nonactive comparators. Small improvements in function and pain with exercise were seen for hip osteoarthritis short term (SOE: low). Functional improvement persisted into intermediate term, but pain improvement did not (SOE: low).

Fibromyalgia: Functional improvements were seen with exercise, mind-body practices, multidisciplinary rehabilitation (SOE: low) and acupuncture (SOE: moderate) short term compared with usual care, attention control, or sham treatment. At intermediate term, there was functional improvement with exercise and acupuncture (SOE: moderate), cognitive-behavioral therapy (CBT), mindfulness-based stress reduction, myofascial release, and multidisciplinary rehabilitation (SOE: low). Long term, functional improvements persisted for multidisciplinary rehabilitation without improvement in pain (SOE: low). Compared with exercise, tai chi conferred improvement in function short and intermediate term (SOE: low). Pain was improved with exercise (short and intermediate term, SOE moderate), and for CBT (short term), mindfulness practices, and multidisciplinary rehabilitation (intermediate term) (SOE low).

Chronic tension headache: Evidence was sparse and the majority of trials were of poor quality. Spinal manipulation resulted in moderate improvement in pain short term.

Conclusions. Trials identified subsequent to the earlier report largely support previous findings—namely that exercise, multidisciplinary rehabilitation, acupuncture, CBT, mindfulness practices, massage, and mind-body practices most consistently improve function and/or pain beyond the course of therapy for specific chronic pain conditions. Additional research, including comparisons with pharmacological and other active controls, on effects beyond the immediate post-treatment period is needed, particularly for conditions other than low back pain.

Keywords 
nonpharmacological treatment chronic pain

Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228

Author/s: 
McDonagh, MS, Selph, SS, Buckley, DI, Holmes, RS, Mauer, K, Ramirez, S, Hsu, FC, Dana, T, Fu, R, Chou

Objectives. To evaluate the effectiveness and comparative effectiveness of nonopioid pharmacologic agents in patients with specific types of chronic pain, considering effects on pain, function, quality of life, and adverse events.

Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, PsycINFO®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) through September 10, 2019, reference lists, data requests, and previous reviews.

Review methods. Randomized controlled trials (RCTs) of nonopioid pharmacologic agents in patients with chronic pain were selected using predefined criteria and dual review. This review focused on seven common chronic pain conditions (neuropathic pain, fibromyalgia, osteoarthritis, inflammatory arthritis, low back pain, chronic headache, sickle cell disease), with effects analyzed at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months). Magnitude of effects were described as small, moderate, or large using previously defined criteria, and strength of evidence was assessed. Meta-analyses were conducted where data allowed, stratified by duration within each intervention type, using random effects models. We evaluated effect modification through subgroup and sensitivity analyses, including specific drug, dose, study quality, and pain type.

Results. We included 185 RCTs in 221 publications and 5 systematic reviews. In the short term, anticonvulsants (pregabalin, gabapentin, and oxcarbazepine for neuropathic pain, pregabalin/gabapentin for fibromyalgia), serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants (duloxetine for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain, milnacipran for fibromyalgia), and nonsteroidal anti-inflammatory drugs (NSAIDs) (for osteoarthritis and inflammatory arthritis) were associated with mostly small improvements (e.g., 5 to 20 points on a 0 to 100 scale) in pain and function. Function was not found to be improved with duloxetine for low back pain or pregabalin/gabapentin for neuropathic pain. Moderate improvement in quality of life was seen with duloxetine in patients with neuropathic pain, and small improvements in patients with osteoarthritis, but evidence was insufficient to draw conclusions for other drugs and conditions. While most comparisons of drugs and doses did not identify differences, diclofenac improved pain and function moderately more than celecoxib. In the intermediate term, limited evidence (1 RCT) showed memantine moderately improved pain, function, and quality of life in patients with fibromyalgia; improvements in pain, but not function, were maintained in the intermediate term with duloxetine and milnacipran for fibromyalgia. Other drugs studied, including acetaminophen (osteoarthritis), capsaicin (neuropathic pain), cannabis (neuropathic pain), amitriptyline (fibromyalgia, neuropathic pain), and cyclobenzaprine (fibromyalgia) had no clear effects. Withdrawal from study due to adverse events was significantly increased with nonopioid drugs, with the greatest increase over placebo seen with cannabis. Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness). Dose viii reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.

Conclusions. In the short term, small improvements in pain and/or function were seen with SNRI antidepressants for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain; pregabalin/gabapentin for neuropathic pain and fibromyalgia; oxcarbazepine for neuropathic pain; and NSAIDs for osteoarthritis and inflammatory arthritis. Improvement in function was not found with duloxetine for low back pain and pregabalin/gabapentin for neuropathic pain. Intermediate- and long-term outcomes were mostly not assessed. Increased incidence of drug class–specific adverse events led to withdrawal from treatment in some patients, suggesting that careful consideration of patient characteristics is needed in selecting nonopioid drug treatments.

Keywords 
chronic pain non-opioid treatment anticonvulsants serotonin-norepinephrine reuptake inhibitor nonsteroidal anti-inflammatory drugs NSAID SNRI cannabis
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