Pain
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Randomized Controlled Trial
Can early oral prolonged-release oxycodone with or without naloxone reduce the duration of epidural analgesia after cystectomy? A 3-arm, randomized, double-blind, placebo-controlled trial.
Thoracic epidural analgesia (TEA) enhances recovery after bowel surgery. Early postoperative prolonged-release oral formulation of oxycodone or oxycodone/naloxone is potentially useful as a second analgesic step to reduce the duration of TEA. We hypothesized that oxycodone would decrease the duration of TEA and combined with naloxone preserve gastrointestinal function. ⋯ In the oxycodone group, we found 8/30 patients with ileus (27%) compared to 2/28 (7%) in the oxycodone/naloxone group and to 2/30 (7%) in the placebo group; (P = 0.031). Oxycodone, with or without naloxone, did not reduce the duration of TEA. Oxycodone alone led to a delayed return of bowel function, whereas the combination was not different from placebo.
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Numerous studies have shown associations between genetic variants and neuropathic pain disorders. Rare monogenic disorders are caused by mutations of substantial effect size in a single gene, whereas common disorders are likely to have a contribution from multiple genetic variants of mild effect size, representing different biological pathways. ⋯ Biobank cohort. Successfully replicated association with a neuropathic pain construct for 2 variants in IL10 underscores the importance of neuroimmune interactions, whereas genome-wide significant association with low back pain (P = 1.3e-8) and false discovery rate 5% significant associations with hip, knee, and neck pain for variant rs7734804 upstream of the MAT2B gene provide evidence of shared contributing mechanisms to overlapping pain conditions at the molecular genetic level.
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Benzodiazepines and opioids are commonly used among veterans suffering from mental health disorders and pain conditions. The objective of this study is to determine whether concomitant benzodiazepine-opioid use increases the incidence of adverse outcomes above the baseline risk of nonacute opioid-only use. The dataset contained all veterans who filled at least 1 opioid prescription during the years 2008 to 2012. ⋯ The final matched sample consisted of 396,141 nonacute opioid-only using veterans and 48,971 concomitant benzodiazepine-opioid users. Receiving opioids and benzodiazepines concomitantly increased the risk of experiencing an adverse outcome with an odds ratio of 1.359 (95% confidence interval: 1.320-1.400; P < 0.0001). Among veterans receiving opioids, concomitant benzodiazepine use is associated with an increased risk of adverse outcomes when compared to the baseline risk of opioid-only using veterans.
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A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn. ⋯ Chromatin-immunoprecipitation assay further confirmed a novel nonhistone modulation function of HDACs on SOX10 expression, that is, HDAC5 regulates SOX10 by binding to the promoter region of Sox10 gene. In conclusion, this study for the first time demonstrates that HDAC5 regulates spinal neuronal sensitization in neuropathic pain by upregulating modulating SOX10 expression. Thus, interventions that reduce HDAC5/SOX10 expression may represent promising avenues in the treatment of neuropathic pain.