Pain
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Conditioned pain modulation (CPM) is assumed to capture endogenous pain modulation. In standard CPM designs, the evaluation of a painful test stimulus (TS) (baseline) is followed by a second evaluation of the TS during/after application of a painful conditioning stimulus (CS) (treatment). However, these standard CPM within designs (baseline always preceding treatment) do not control for order effects, which might help to distinguish specific CPM inhibition from general habituation. ⋯ Only the standard CPM order (baseline before treatment) yielded robust pain inhibition effects, whereas the reversed order (treatment before baseline) led to no modulation or seeming pain facilitation. Because control for order effects is otherwise mandatory in within designs, it is surprising that it has been neglected in standard CPM protocols. Finding pain inhibition only in the standard CPM order suggests that CPM inhibition is at least partially confounded with habituation.
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Neuropathic pain (NP) is a chronic condition caused by nerve injuries, such as nerve compression. Understanding its underlying neurobiological mechanisms is critical for developing effective treatments. Previous studies have shown that Kinesin family member 1A (Kif1a) heterozygous deficient mice display sensory deficits in response to nociceptive stimuli. ⋯ Furthermore, TET1 knockdown or overexpression significantly affected pain-related behaviors, as well as Kif1a methylation and transcription. Female mice given intrathecal injections of PI3K inhibitors exhibited similar molecular and behavioral outcomes as male mice. These findings offer new insights into NP mechanisms, suggesting that targeting the PI3K/KIF1A axis could be a promising therapeutic approach for NP treatment.
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Exosomes served as "communicators" to exchange information among different cells in the nervous system. Our previous study demonstrated that the enhanced spinal synaptic transmission contributed to chronic visceral pain in irritable bowel syndrome. However, the underlying mechanism of primary sensory neuron (PSN)-derived exosomes on spinal transmission remains unclear. ⋯ The PSN-derived exosomal miR-1306-3p sorted from spinal dorsal horn activated P2X3R, enhanced spinal synaptic transmission, and led to visceral pain in NMD mice. Moreover, upregulation of Rab27a in dorsal root ganglia mediated the increased release of PSN-derived exosomes, and intrathecal injection of siR-Rab27a reduced visible PSN-derived exosomes in spinal cord, suppressed spinal synaptic transmission, and alleviated visceral pain in NMD mice. This and future studies would reveal the detailed mechanisms of PSN-derived exosomes and provide a potential target for clinical treatment of chronic visceral pain in patients with irritable bowel syndrome.
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Chronic musculoskeletal pain (CMP) causes significant health loss worldwide and is one of the major public health issues of our time. Cigarette smoking is an independent risk factor of CMP. The present study examined the potential mediating role of 2 subproducts of cigarette smoke, acrylamide and cadmium, individually and combined, on the association between cigarette smoking and CMP, using the Inverse Odds Ratio Weighting (IORW) method. ⋯ Small indirect effects were identified through acrylamide (aOR = 1.24 [95% CI: 0.96-1.61]) and cadmium (aOR = 1.56 [95% CI: 0.92-2.63]) only among moderate and heavy smokers. When both biomarkers were considered together, their indirect effect was larger (aOR = 2.07 [95% CI: 1.32-3.23]). These results suggest that the association between cigarette smoking and CMP is mediated by acrylamide and cadmium and that these substances, also present in food and the environment, may serve as biomarkers of CMP.
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We developed the National Institutes of Health helping to end addiction long-term initiative morphine milligram equivalent (MME) calculator to standardize MME calculations across pain research studies, addressing a critical barrier to effective research synthesis and meta-analysis. The tool provides evidence-based mapping factors for 29 opioids through a research electronic data capture-based calculator and companion Web site (research-mme.wakehealth.edu). Development involved systematic evidence evaluation of literature from 1949 to March 2024, following PRISMA guidelines. ⋯ The calculator features options to analyze results with or without buprenorphine, accommodating its emerging role in pain research. This standardized framework enables researchers to map opioid doses using consistent, evidence-based ratios and harmonize data collection across research networks. While the tool represents a significant advance in standardizing MME calculations for research, limitations in the underlying evidence base highlight the need for continued validation through clinical research.