Pain
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Growing evidence suggests that leukocyte extravasation is initiated by the interaction of selectins with their ligands; as well as an essential role for P-selectin in the initial recruitment of inflammatory cells to sites of inflammation. In this study, P-selectin-deficient (P-sel-/-) mice were used to test the hypothesis that lack of P-selectin would attenuate the recruitment of inflammatory cells to the site of inflammation, thereby modulating pain in a murine chronic neuropathic pain model. Nociceptive sensitization and the microenvironment of the peripheral injury site were studied in wild-type (P-sel+/+) and P-selectin-deficient (P-sel-/-) mice after partial sciatic nerve ligation (PSNL). ⋯ In addition, endogenous opioid peptides mRNA was significantly lower in P-sel-/- mice compared with P-sel +/+ mice. The current results demonstrated that the absence of P-selectin in mice leads to an altered microenvironment that attenuated behavioral hypersensitivity. The specific role of P-selectin could have been a result of decreased neutrophils, as well as the accumulation of macrophages at the site of injury, which may subsequently modulate the inflammatory cytokine expression and impact behavioral hypersensitivity within the injured nerve.
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We previously discovered that when faced with a challenging cognitive task in the context of pain, some people prioritize task performance, while in others, pain results in poorer performance. These behaviours, designated respectively as A- and P-types (for attention dominates vs pain dominates), may reflect pain coping strategies, resilience or vulnerabilities to develop chronic pain, or predict the efficacy of treatments such as cognitive behavioural therapy. Here, we used a cognitive interference task and pain stimulation in 80 subjects to interrogate psychophysical, psychological, brain structure and function that distinguish these behavioural strategies. ⋯ Brain imaging revealed structural and functional brain features that characterized these behavioural strategies. Compared to the performance-oriented A group, the P group had (1) more gray matter in regions implicated in pain and salience (anterior insula, anterior midcingulate cortex, supplementary motor area, orbitofrontal cortex, thalamus, caudate), (2) greater functional connectivity in sensorimotor and salience resting-state networks, (3) less white matter integrity in the internal and external capsule, anterior thalamic radiation and corticospinal tract, but (4) were indistinguishable based on sex, pain sensitivity, neuroticism, and pain catastrophizing. These data may represent neural underpinnings of how task performance vs pain is prioritized and provide a framework for developing personalized pain therapy approaches that are based on behaviour-structure-function organization.
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Chronic pain often accompanies immune responses and immune cells are known to be involved in chronic pain. Store-operated calcium (SOC) channels are calcium-selective cation channels and play an important role in the immune system. YM-58483, a potent SOC channel inhibitor, has been shown to inhibit cytokine production from immune cells and attenuate antigen-induced hypersensitivity reactions. ⋯ YM-58483 diminished CFA-induced paw edema, and reduced production of TNF-α, IL-1β and PGE2 in the CFA-injected paw. In vitro, SOC entry in nociceptors was more robust than in nonnociceptors, and the inhibition of SOC entry by YM-58483 in nociceptors was much greater than in nonnociceptors. Our findings indicate that YM-58483 is a potent analgesic and suggest that SOC channel inhibitors may represent a novel class of therapeutics for pain.
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This article reports the development of natural history and active treatment benchmarks for psychological treatments of chronic pain. The benchmarks were derived from randomized controlled trials (RCTs) reported in a published meta-analysis. In two preliminary studies we surveyed small samples of active clinicians working in U. ⋯ The average ES across outcome domains for the treatment arms was approximately 0.35. These benchmarks may be used to assess the effectiveness of routine clinical treatments for chronic pain. The application of these data and the limitations of the study are discussed.