Pain
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We investigated the association of chronic pain with physical and mental comorbidity in the New Zealand population by measuring chronic pain status separate from comorbid conditions. Models of allostatic load provided a conceptual basis for considering multi-morbidity as accumulated comorbid load and for using both discrete conditions and cumulative measures in analyses. The nationally representative cross-sectional survey data included self-reported doctor-diagnosed chronic physical and mental health conditions, Kessler 10-item scale scores, an independent measure of chronic pain, and sociodemographic characteristics. ⋯ This synergistic effect is not apparent for other conditions or for additional comorbid load. Results imply that measurement of chronic pain independent of comorbid conditions and adjustment for comorbid conditions is important for more accurate prevalence estimates and understanding relationships between conditions. Future epidemiological research might usefully incorporate independent measurement of chronic pain alongside adjustment for specific physical and mental health conditions as well as accumulated comorbid load.
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The complement system is an important part of innate immunity. Complement activation generates a set of effector molecules with diverse biological functions. C5a is a crucial terminal component of the complement cascade. ⋯ The main findings were: (1) Heat vs mechanical nociceptive sensitization after incision were differentially reduced in C5aR(-/-) mice, with thermal sensitization affected throughout the postincisional period but mechanical sensitization affected only at later time points; (2) Edema developed after incision in wild-type mice but only slightly and transiently in C5aR(-/-) mice, and (3) Deletion of C5aR blocked interleukin-1β and nerve growth factor production near the wound site. These findings demonstrate that the complement system component C5a is a novel biomarker and mediator associated with postsurgical nociceptive processing. C5aR may provide a novel target for the control of pain and inflammation after surgery.
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We have recently found that, following complete Freund's adjuvant (CFA)-induced inflammation, cutaneous polymodal nociceptors (CPM) lacking the transient receptor potential vanilloid 1 (TRPV1) are sensitized to heat stimuli. In order to determine possible mechanisms playing a role in this change, we examined gene expression in the L2/L3 sensory ganglia following CFA injection into the hairy hind paw skin and found that G-protein-coupled purinoreceptor P2Y1 expression was increased. This receptor is of particular interest, as most CPMs innervating mouse hairy skin bind isolectin B4, which co-localizes with P2Y1. ⋯ Surprisingly, inhibition of P2Y1 during inflammation also significantly increased the number of CPM neurons expressing TRPV1 without a change in the total number of TRPV1-positive cells in the L2 and L3 dorsal root ganglia. These results show that the inflammation-induced enhanced expression of P2Y1 is required for normal heat sensitization of cutaneous CPM fibers. They also suggest that P2Y1 plays a role in the maintenance of phenotype in cutaneous afferent fibers containing TRPV1.
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Effector CD4(+) T lymphocytes generated in response to antigens produce endogenous opioids. Thus, in addition to their critical role in host defenses against pathogens, effector CD4(+) T lymphocytes contribute to relieving inflammatory pain. In this study, we investigated mechanisms of opioid release by antigen-experienced effector CD4(+) T cells that leave draining lymph nodes and come back into the inflammatory site. ⋯ Analgesia was observed by transferring effector CD4(+) T lymphocytes with Th1 or Th2 phenotype, suggesting that antinociceptive activity is a fundamental property of effector CD4(+) T lymphocytes irrespective of their effector functions. Based on the use of agonists and antagonists selective for each of the opioid receptor subclasses, we showed that analgesia induced by T cell-derived opioids is elicited via activation of δ-type opioid receptors in the periphery. Thus, the antinociceptive activity is a fundamental property associated with the effector phase of adaptive immunity, which is driven by recognition of the cognate antigen by effector CD4(+) T lymphocytes at the inflammatory site.