Pain
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The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. ⋯ Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.
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Observational Study
Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study.
N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. ⋯ Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group ( P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.
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Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide- co -glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion. ⋯ Altered central neuropathic pain mechanisms during this period are limited to reduced innate immune cell cytokine expression. However, in the chronic phase of SCI, nanoparticle treatment induces changes in both central and peripheral neuropathic pain signaling, driving reductions in cytokine production and other immune-relevant markers. This research suggests that drug-free PLG nanoparticles reprogram peripheral proalgesic pathways subacutely after SCI to reduce neuropathic pain outcomes and improve chronic central pain signaling.
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Meta Analysis
Psychological treatments for the management of pain after musculoskeletal injury: a systematic review and meta-analysis.
Musculoskeletal injury is a leading cause of pain and disability worldwide; 35% to 75% of people experience persistent pain for months and years after injury. Psychological treatments can reduce pain, functional impairment, and psychological distress but are not widely used after injury. This systematic review and meta-analysis (PROSPERO ID: CRD42021236807) aimed to synthesize the literature testing psychological treatments for pain after musculoskeletal injury. ⋯ Most studies had risk of bias domains judged to be high or unclear. Owing to very low certainty of results, we are unsure whether psychological therapies reduce pain and functional impairment after musculoskeletal injury; they may result in improved depression immediately posttreatment and at follow-up. More research is needed to identify treatments that result in enduring effects.