The journal of pain : official journal of the American Pain Society
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Blood nerve barrier disruption and edema are common in neuropathic pain as well as in complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. ⋯ Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. PERSPECTIVE: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors.
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This systematic review and meta-analysis investigated the effectiveness of physical activity (PA) and sedentary behavior (SB) interventions on PA and SB levels in people with persistent musculoskeletal pain. We explored the effectiveness of behavior change techniques (BCTs), the use of behavior change theory and non-PA/SB outcomes. Randomized controlled trials of PA or SB interventions for people with persistent musculoskeletal pain were eligible. ⋯ PROSPERO registration: CRD42020180260. PERSPECTIVE: This review investigated the effects of physical activity and sedentary behavior interventions on physical activity and sedentary behavior levels in people with persistent musculoskeletal pain. Current evidence shows a modest benefit for interventions on physical activity post-intervention but not at longer-term follow-up or on sedentary behavior at any time-point, however quality of evidence is low to very low.
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Native Americans (NAs) have higher pain rates than the general U. S. population. It has been found that increased central sensitization and reduced pain inhibition are pronociceptive processes that increase pain risk; yet, little attention has focused on the influence of psychosocial factors. ⋯ This indicates experienced discrimination may promote a pain risk phenotype in NAs that involves spinal sensitization resulting from impaired inhibition of spinal nociception without sensitization of pain experience. PERSPECTIVE: This study found that discrimination was associated with spinal sensitization and impaired descending inhibition of spinal nociception. These findings bolster our understanding of how social stressors experienced disproportionately by minoritized groups can contribute to pain outcomes.
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Opioid-induced hyperalgesia (OIH) is a problem associated with prolonged use of opioids in chronic pain management, and its effective treatment has been hampered by lack of mechanistic evidence. Oligodendrocytes have recently been linked with several pain-related diseases; however, little is known its role in OIH. The prelimbic medial prefrontal cortex (PL-mPFC) has emerged as a significant center of pain regulation, and is rich in oligodendrocytes. ⋯ We suggest that OIH may be primed in part via oligodendrocyte apoptosis in the PL-mPFC. PERSPECTIVE: In this study we showed that oligodendrocyte apoptosis in the PL-mPFC is a key trigger for fentanyl-induced hyperalgesia. Targeting oligodendrocyte apoptosis in the PL-mPFC may prevented hyperalgesia priming induced by fentanyl.