Pain
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Multicenter Study
Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.
α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. ⋯ In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.
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Review Meta Analysis
Racial and ethnic differences in experimental pain sensitivity: Systematic review and meta-analysis.
Our objective was to describe the racial and ethnic differences in experimental pain sensitivity. Four databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO) were searched for studies examining racial/ethnic differences in experimental pain sensitivity. Thermal-heat, cold-pressor, pressure, ischemic, mechanical cutaneous, electrical, and chemical experimental pain modalities were assessed. ⋯ Estimates did not vary by pain modalities, nor by other demographic factors; however, SMDs were significantly different based on the sample size. Racial/ethnic differences in experimental pain sensitivity were more pronounced with suprathreshold than with threshold stimuli, which is important in clinical pain treatment. Additional studies examining mechanisms to explain such differences in pain tolerance and pain ratings are needed.
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Randomized Controlled Trial Multicenter Study
Persistent pain after motor vehicle collision: comparative effectiveness of opioids vs nonsteroidal antiinflammatory drugs prescribed from the emergency department-a propensity matched analysis.
Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. ⋯ However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.
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Alterations in amygdala activity are apparent in women who report a history of early life stress (ELS) and those diagnosed with chronic pain disorders. Chronic stress in adulthood induces visceral hypersensitivity by alterations in glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) expression within the central amygdala (CeA). Here, we hypothesized that unpredictable ELS, previously shown to induce visceral hypersensitivity in adult female rats, alters GR and CRF expression in the CeA. ⋯ Knockdown of GR increased visceral sensitivity in all rats but revealed an exaggerated visceral hypersensitivity in females with a history of predictable or unpredictable ELS compared with that of controls. Knockdown of CRF expression or antagonism of CRF1R in the CeA attenuated visceral hypersensitivity after unpredictable ELS. This study highlights a shift in GR and CRF regulation within the CeA after ELS that underlies the development of visceral hypersensitivity in adulthood.
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We aimed to evaluate the effect of pain education on opioid prescribing by early-career general practitioners. A brief training workshop was delivered to general practice registrars of a single regional training provider. The workshop significantly reduced "hypothetical" opioid prescribing (in response to paper-based vignettes) in an earlier evaluation. ⋯ There was some evidence of a reduction in initial opioid prescriptions in the training group (interaction odds ratio: 0.74; 95% CI: 0.48-1.16; P value 0.19). This brief training package failed to increase overall opioid cessation. The inconsistency of these actual prescribing results with "hypothetical" prescribing behavior suggests that reducing opioid prescribing in chronic noncancer pain requires more than changing knowledge and attitudes.