Opioid use and social disadvantage in patients with chronic musculoskeletal pain.

BACKGROUND: Historically, marginalized patients were prescribed less opioid medication than affluent, white patients. However, because of persistent differential access to nonopioid pain treatments, this direction of disparity in opioid prescribing may have reversed. OBJECTIVE: To compare social disadvantage and health in patients with chronic pain who were managed with versus without chronic opioid therapy. It was hypothesized that patients routinely prescribed opioids would be more likely to live in socially disadvantaged communities and report worse health. DESIGN: Cross-sectional analysis of a retrospective cohort defined from medical records from 2000 to 2019. SETTING: Single tertiary safety net medical center. PATIENTS: Adult patients with chronic musculoskeletal pain who were managed longitudinally by a physiatric group practice from at least 2011 to 2015 (n = 1173), subgrouped by chronic (≥4 years) adherent opioid usage (n = 356) versus no chronic opioid usage (n = 817). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was the unadjusted between-group difference in social disadvantage, defined by living in the worst national quartile of the Area Deprivation Index (ADI). An adjusted effect size was also calculated using logistic regression, with age, sex, race, and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function scores as covariates. Secondary outcomes included adjusted differences in health by chronic opioid use (measured by PROMIS). RESULTS: Patients managed with chronic opioid therapy were more likely to live in a zip code within the most socially disadvantaged national quartile (34.9%; 95% confidence interval [CI] 29.9-39.9%; vs. 24.9%; 95% CI 21.9-28.0%; P < .001), and social disadvantage was independently associated with chronic opioid use (odds ratio [OR] 1.01 per ADI percentile [1.01-1.02]). Opioid use was also associated with meaningfully worse PROMIS Depression (3.8 points [2.4-5.1]), Anxiety (3.0 [1.4-4.5]), and Pain Interference (2.6 [1.7-3.5]) scores. CONCLUSIONS: Patients prescribed chronic opioid treatment were more likely to live in socially disadvantaged neighborhoods, and chronic opioid use was independently associated with worse behavioral health. Improving access to multidisciplinary, nonopioid treatments for chronic pain may be key to successfully overcoming the opioid crisis.

The Influence of Race, Sex, and Social Disadvantage on Self-reported Health in Patients Presenting With Chronic Musculoskeletal Pain.

OBJECTIVE: The aim of the study was to better address sociodemographic-related health disparities. This study examined which sociodemographic variables most strongly correlate with self-reported health in patients with chronic musculoskeletal pain. DESIGN: This single-center, cross-sectional study examined adult patients, followed by a physiatrist for chronic (≥4 yrs) musculoskeletal pain. Sociodemographic variables considered were race, sex, and disparate social disadvantage (measured as residential address in the worst vs. best Area Deprivation Index national quartile). The primary comparison was the adjusted effect size of each variable on physical and behavioral health (measured by Patient-Reported Outcomes Measurement Information System [PROMIS]). RESULTS: In 1193 patients (age = 56.3 ± 13.0 yrs), disparate social disadvantage was associated with worse health in all domains assessed (PROMIS Physical Function Β = -2.4 points [95% confidence interval = -3.8 to -1.0], Pain Interference = 3.3 [2.0 to 4.6], Anxiety = 4.0 [1.8 to 6.2], and Depression = 3.7 [1.7 to 5.6]). Black race was associated with greater anxiety than white race (3.2 [1.1 to 5.3]), and female sex was associated with worse physical function than male sex (-2.5 [-3.5 to -1.5]). CONCLUSIONS: Compared with race and sex, social disadvantage is more consistently associated with worse physical and behavioral health in patients with chronic musculoskeletal pain. Investment to ameliorate disadvantage in geographically defined communities may improve health in sociodemographically at-risk populations.

In vivo identification of small molecules mediating Gpr126/Adgrg6 signaling during Schwann cell development.

Gpr126/Adgrg6, an adhesion family G protein-coupled receptor (aGPCR), is required for the development of myelinating Schwann cells in the peripheral nervous system. Myelin supports and insulates vertebrate axons to permit rapid signal propagation throughout the nervous system. In mammals and zebrafish, mutations in Gpr126 arrest Schwann cells at early developmental stages. We exploited the optical and pharmacological tractability of larval zebrafish to uncover drugs that mediate myelination by activating Gpr126 or functioning in parallel. Using a fluorescent marker of mature myelinating glia (Tg[mbp:EGFP-CAAX]), we screened hypomorphic gpr126 mutant larvae for restoration of myelin basic protein (mbp) expression along peripheral nerves following small molecule treatment. Our screens identified five compounds sufficient to promote mbp expression in gpr126 hypomorphs. Using an allelic series of gpr126 mutants, we parsed the ability of small molecules to restore mbp, suggesting differences in drug efficacy dependent on Schwann cell developmental state. Finally, we identify apomorphine hydrochloride as a direct small molecule activator of Gpr126 using combined in vivo/in vitro assays and show that aporphine class compounds promote Schwann cell development in vivo. Our results demonstrate the utility of in vivo screening for aGPCR modulators and identify small molecules that interact with the gpr126-mediated myelination program.