Trends in U.S. Medical Cannabis Registrations, Authorizing Clinicians, and Reasons for Use From 2020 to 2022.

BACKGROUND: As medical cannabis availability increases, up-to-date trends in medical cannabis licensure can inform clinical policy and care. OBJECTIVE: To describe current trends in medical cannabis licensure in the United States. DESIGN: Ecological study with repeated measures. SETTING: Publicly available state registry data from 2020 to 2022. PARTICIPANTS: People with medical cannabis licenses and clinicians authorizing cannabis licenses in the United States. MEASUREMENTS: Total patient volume and prevalence per 10 000 persons in the total population, symptoms or conditions qualifying patients for licensure (that is, patient-reported qualifying conditions), and number of authorizing clinicians. RESULTS: In 2022, of 39 jurisdictions allowing medical cannabis use, 34 reported patient numbers, 19 reported patient-reported qualifying conditions, and 29 reported authorizing clinician numbers. Enrolled patients increased 33.3% from 2020 (3 099 096) to 2022 (4 132 098), with a corresponding 23.0% increase in the population prevalence of patients (175.0 per 10 000 in 2020 to 215.2 per 10 000 in 2022). However, 13 of 15 jurisdictions with nonmedical adult-use laws had decreased enrollment from 2020 to 2022. The proportion of patient-reported qualifying conditions with substantial or conclusive evidence of therapeutic value decreased from 70.4% (2020) to 53.8% (2022). Chronic pain was the most common patient-reported qualifying condition in 2022 (48.4%), followed by anxiety (14.2%) and posttraumatic stress disorder (13.0%). In 2022, the United States had 29 500 authorizing clinicians (7.7 per 1000 patients), 53.5% of whom were physicians. The most common specialties reported were internal or family medicine (63.4%), physical medicine and rehabilitation (9.1%), and anesthesia or pain (7.9%). LIMITATION: Missing data (for example, from California), descriptive analysis, lack of information on individual use patterns, and changing evidence base. CONCLUSION: Enrollment in medical cannabis programs increased overall but generally decreased in jurisdictions with nonmedical adult-use laws. Use for conditions or symptoms without a strong evidence basis continues to increase. Given these trends, more research is needed to better understand the risks and benefits of medical cannabis. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse of the National Institutes of Health.

Effects of scapular treatment on chronic neck pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic neck pain (CNP) is a common public health problem that affects daily living activities and quality of life. There is biomechanical interdependence between the neck and scapula. Studies have shown that shoulder blade function might be related to chronic neck pain. We therefore evaluated the effects of scapular targeted therapy on neck pain and function in patients with CNP. METHODS: Databases, including MEDLINE (via PubMed), EMBASE (via Ovid), Ovid, Web of Science, and Scopus, were systematically searched for randomized controlled trials published in English investigating treatment of the scapula for CNP before July 16, 2023. RESULTS: A total of 313 participants were included from 8 RCTs. Compared with those in the control group, the intervention in the scapular treatment group exhibited greater improvement in pain intensity (standardized mean difference (SMD) = 2.55; 95% CI = 0.97 to 4.13; P = 0.002), with moderate evidence. Subgroup analysis for pain intensity revealed a significant difference between the sexes, with only the female population (SMD = 6.23, 95% CI = 4.80 to 7.65) showing better outcomes than those with both sexes (SMD = 1.07, 95% CI = 0.57 to 1.56) (p < 0.00001). However, moderate evidence demonstrated no improvement in neck disability after scapular treatment (SMD of 0.24[-0.14, 0.62] of Neck Disability Index or Northwick Park Neck Pain Questionnaire). No effect of scapular treatment was shown on the pressure pain threshold (PPT). The cervical range of motion (CROM) and electromyographic activity of neck muscles could not be conclusively evaluated due to limited support in the articles, and further study was needed. However, the patient's head forward posture appeared to be corrected after scapular treatment. CONCLUSION: Scapular therapy was beneficial for relieving pain intensity in patients with CNP, especially in women. Head forward posture might also be corrected with scapular therapy. However, scapular therapy may have no effect on the PPT or neck disability. However, whether scapular therapy could improve CROM and cervical muscle activation in patients with CNPs had not been determined and needed further study.

Case Report: An Unexpected Complication of Intrathecal Therapy.

Traditionally, intrathecal therapy has been used for pain amelioration in cancer patients, but now has indications for nonmalignant chronic pain conditions. Due to its expanding use, it is imperative to understand the risks and management of intrathecal pump implantation. This case illustrates a series of uncommon intrathecal pump complications in a 52-year-old woman with complex regional pain syndrome. Considering the complications outlined in this case, there is a need to conduct retrospective studies and establish guidelines to address when it is optimal to remove a chronically placed catheter as well as the proper technique for removal.

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors. Compared with wild-type mice, Comt+/- mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting >3 months. Comt+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (≥12 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype × stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.

Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER: NCT02560545.

Predictors of success of pharmacological management in patients with chronic lower back pain: systematic review.

BACKGROUND: Conservative management is recommended as the first therapeutic step in chronic low back pain (LBP), but there is no available evidence regarding the possible effect of patients' baseline characteristics on the therapeutic outcomes. A systematic review of the literature was performed to investigate this point. METHODS: In February 2024, all the level I studies investigating the role of pharmacological management for chronic LBP were accessed. Data concerning the patient demographic at baseline were collected: number of patients and related mean BMI and age, duration of the symptoms, duration of the follow-up, percentage of females, Numeric Rating Scale (NRS), the Roland Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI). The outcomes at the last follow-up were evaluated through NRS, RMQ, and ODI. A multiple linear model regression diagnostic through the Pearson Product-Moment Correlation Coefficient (r) was used. RESULTS: Data from 47 articles (9007 patients) were obtained. The analysis yielded the following significant associations: age at baseline and NRS at follow-up (r = - 0.22; P = 0.04), NRS at baseline with NRS (r = 0.26; P = 0.03) and RMQ (r = - 0.58; P = 0.02) at follow-up, RMQ at baseline and the same at follow-up (r = 0.69; P = 0.0001). CONCLUSION: Older age, higher BMI, presence of comorbidities, higher ODI and a long history of symptoms or surgical treatments do not reduce the efficacy of pharmacological management of chronic LBP. However, pharmacological therapy is not an effective option for patients with high baseline RMQ. LEVEL OF EVIDENCE: I systematic review of RCTs.

Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) frequently experience chronic pain due to the limited effectiveness and safety profiles of current analgesics. Understanding the molecular and synaptic mechanisms underlying abnormal neuronal activation along the pain signaling pathway is essential for developing new analgesics to address SLE-induced chronic pain. Recent studies, including those conducted by our team and others using the SLE animal model (MRL/lpr lupus-prone mice), have unveiled heightened excitability in nociceptive primary sensory neurons within the dorsal root ganglia and increased glutamatergic synaptic activity in spinal dorsal horn neurons, contributing to the development of chronic pain in mice with SLE. Nociceptive primary sensory neurons in lupus animals exhibit elevated resting membrane potentials, and reduced thresholds and rheobases of action potentials. These changes coincide with the elevated production of TNFα and IL-1ß, as well as increased ERK activity in the dorsal root ganglion, coupled with decreased AMPK activity in the same region. Dysregulated AMPK activity is linked to heightened excitability in nociceptive sensory neurons in lupus animals. Additionally, the increased glutamatergic synaptic activity in the spinal dorsal horn in lupus mice with chronic pain is characterized by enhanced presynaptic glutamate release and postsynaptic AMPA receptor activation, alongside the reduced activity of glial glutamate transporters. These alterations are caused by the elevated activities of IL-1ß, IL-18, CSF-1, and thrombin, and reduced AMPK activities in the dorsal horn. Furthermore, the pharmacological activation of spinal GPR109A receptors in microglia in lupus mice suppresses chronic pain by inhibiting p38 MAPK activity and the production of both IL-1ß and IL-18, as well as reducing glutamatergic synaptic activity in the spinal dorsal horn. These findings collectively unveil crucial signaling molecular and synaptic targets for modulating abnormal neuronal activation in both the periphery and spinal dorsal horn, offering insights into the development of analgesics for managing SLE-induced chronic pain.

Compounded Pain Formulations: What is the Evidence?

Pain syndromes are among the most widespread, costly, and debilitating of all neurological disorders. The number of patients living with chronic pain is expected to increase with the aging population and with the rise in obesity and diabetes across the nation. This type of pain is often insensitive to the traditional pain pharmacopeia or surgical intervention. Over the last 10 years the number of prescriptions that have been compounded by pharmacists has increased dramatically. There are a number of drugs in the area of pain management that have been formulated and compounded by pharmacists to treat conditions such as diabetic neuropathy, fibromyalgia, postherpetic neuralgia, joint pain, arthritis, and a variety of other conditions. A significant portion of these compounded analgesic preparations is made up of topical/transdermal dosage forms such as gels and creams. While the efficacy and doses of these drugs in systemic dosage forms have been widely established, little is known about the permeation and efficacy of these compounds from topical/transdermal gels. This review will provide an overview of chronic pain as a disease, the mechanisms of chronic pain, current treatment approaches to chronic pain, and a discussion of the drugs that are typically compounded into these topical formulations and studied in clinical trials.

Chronic Low Back Pain in Adults: Evaluation and Management.

Chronic low back pain, defined as lumbar pain persisting for 12 weeks or more, occurs in about 13% of U.S. adults. Patients with chronic low back pain should have a history and physical examination to identify red flags that may indicate serious conditions that warrant immediate intervention or yellow flags (i.e., psychological, environmental, and social factors) that indicate risk of disability. The examination should include an evaluation for radicular symptoms. Routine imaging is not recommended but is indicated when red flags are present, there is a neuromuscular deficit, or if pain does not resolve with conservative therapy. Patients should avoid bed rest. Nonpharmacologic treatment is first-line management and may include therapies with varying evidence of support, such as counseling, exercise therapy, spinal manipulation, massage, heat, dry needling, acupuncture, transcutaneous electrical nerve stimulation, and physical therapy. Pharmacologic interventions are second-line treatment. Nonsteroidal anti-inflammatory drugs are the initial medication of choice; duloxetine may also be beneficial. Evidence is inconclusive to recommend the use of benzodiazepines, muscle relaxants, antidepressants, corticosteroids, insomnia agents, anticonvulsants, cannabis, acetaminophen, or long-term opioids. Epidural corticosteroid injections are not recommended except for short-term symptom relief in patients with radicular pain. Most patients with chronic low back pain will not require surgery; evaluation for surgery may be considered in those with persistent functional disabilities and pain from progressive spinal stenosis, worsening spondylolisthesis, or herniated disk. Physicians should consider prevention of chronic low back pain when patients present with acute back pain. Screening tools are available to predict the progression from acute to chronic low back pain, and targeted treatment strategies are beneficial for preventing progression.

Older Adult and Primary Care Practitioner Perspectives on Using, Prescribing, and Deprescribing Opioids for Chronic Pain.

Importance: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations. Objective: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing. Design, Setting, and Participants: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs. Main Outcome and Measures: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing. Results: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance. Conclusions and Relevance: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay. RESULTS: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway. CONCLUSIONS: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.

The Effect of Veteran Status and Chronic Pain on Past 30-Day Sedative Use Among Community-Dwelling Adult Males.

INTRODUCTION: Given the high sedative prescription rate, the sedative-associated morbidity, and mortality nationally (especially among veterans), we aimed to test the hypothesis that veteran status in the presence of chronic pain would be associated with greater sedative use when compared with nonveteran status. METHODS: The study participants were recruited by Community Health Workers (CHWs) through the ongoing community engagement program (HealthStreet) at the University of Florida. CHWs collected information on sociodemographic factors, health status, and past 30-day drug use patterns. RESULTS: The study sample comprised 4,732 male participants, of which 21% were veterans, 58% were Blacks and 8.4% had used prescription sedatives in the past 30 days. Veterans (vs nonveterans) were twice as likely to have used prescription sedatives in the past 30 days in the presence of chronic pain. CONCLUSIONS: Veterans with chronic pain are a high-risk population for current prescription sedative use.

Effect of a Multidisciplinary Review Panel on Daily Morphine Milligram Equivalents for Patients With Chronic Pain.

INTRODUCTION/OBJECTIVE: Physicians and other health care professionals are challenged regularly to balance managing pain for patients with chronic pain receiving chronic opioid therapy (COT) with following the national guidelines and standards regarding daily morphine milligram equivalents (MME). This quality improvement project aimed to determine the effect of referral to a multidisciplinary review panel on daily MME for patients receiving COT for chronic pain. METHODS: This quality improvement project included patients who had an established relationship with a primary care or community internal medicine clinician at a large health care organization and were referred to a newly created multidisciplinary review panel for their recommendations regarding treatment of pain. Criteria for patient referral were diagnosis of a chronic, painful condition, and use of chronic opioid medications. These patients were selected and referred at the discretion of their primary care clinician from January 2, 2019, through December 31, 2020. Data for this project were collected at the time of initial referral to the panel and 6 months after recommendations. The daily MME were assessed at the 2 time points. RESULTS: Thirteen patients were referred to the review panel during the project period. The median daily MME at the time of referral was 180. Daily MME decreased by a median of 14 MME after 6 months. The MME did not increase during the project period for any participants. CONCLUSIONS: Referral of patients receiving COT to a multidisciplinary review panel may reduce their daily opioid dose.

Definición de la fibromialgia / Definition of fibromyalgia

El artículo define brevemente la fibromialgia dentro de un contexto más amplio incluyendo las raíces históricas del concepto y su posible etiología, así como su interpretación dentro de los modelos biopsicosociales más actuales, con implicaciones terapéuticas de alto interés.(AU)

Chronic opioid pain treatment converted to buprenorphine: A case series using a 3-step low-dose incremental dosing guideline.

We report a 30-case series from the Pain Management Center at the Massachusetts General Hospital where we have applied a guideline to convert chronic treatment for pain from full agonist opioids (FAO) to buprenorphine (BUP). Of the patients, 24 (80 percent) elected to continue BUP over FAO. Five conversions were stopped for side effects (fatigue) and/or lack of sufficient pain reduction. One patient elected not to participate on the day that the conversion was to begin. There were no major adverse events. We conclude that conversion to BUP should be considered as an alternative to treat patients on chronic opioids for pain.

Examining the relationship between head trauma and opioid use disorder: A systematic review.

OBJECTIVE: To examine recent literature and determine common clinical risk factors between antecedent traumatic brain injury (TBI) and the following development of opioid misuse and provide a framework for clinical identification of at-risk subjects and evaluate potential treatment implications within this association. DESIGN: A comprehensive systematic literature search of PubMed was conducted for articles between 2000 and December 2022. Studies were included if the human participant had any head trauma exposure and any chronic opioid use or dependence. After eligibility criteria were applied, 16 studies were assessed for thematic trends. RESULTS: Opioid use disorder (OUD) risks are heightened in cohorts with head trauma exposed to opioids while in the hospital, specifically with tramadol and oxycodone. Chronic pain was the most common predictor of long-term OUD, and continuous somatic symptoms associated with the TBI can lead to long-term opioid usage. Individuals who present with coexisting psychiatric conditions pose significantly more risk associated with a higher risk of long-term opioid use. CONCLUSION: Findings indicate that therapists and clinicians must consider a risk profile for persons with TBI and follow an integrated care approach to account for mental health, prior substance misuse, presenting somatic symptoms, and current medication regimen during evaluation.

A novel microglia-targeting strategy based on nanoparticle-mediated delivery of miR-26a-5p for long-lasting analgesia in chronic pain.

Accumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions.

Pain Management in Burn Patients: Pharmacologic Management of Acute and Chronic Pain.

Burn-related pain can contribute to decreased quality of life and long-term morbidity, limiting functional recovery. Burn-related pain should be assessed first by chronicity (acute or chronic), followed by type (nociceptive, neuropathic, nociplastic), to guide multimodal pharmacologic management in a stepwise algorithm approach. Combination therapies increase the efficacy and reduce toxicity by offering a multimodal approach that targets different receptors in the peripheral nervous system and central nervous system. When multimodal pharmacologic management is ineffective, etiologies of burn-related pain amenable to surgical interventions must be considered. It is important to know when to refer a patient to pain management.

A multi-ancestry genetic study of pain intensity in 598,339 veterans.

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the genome-wide association studies findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, ß-blockers and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.