The journal of pain : official journal of the American Pain Society
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High molecular weight hyaluronan (HMWH), a prominent component of the extracellular matrix binds to and signals via multiple receptors, including cluster of differentiation 44 (CD44) and toll-like receptor 4 (TLR4). We tested the hypothesis that, in the setting of inflammation, HMWH acts at TLR4 to attenuate hyperalgesia. We found that the attenuation of prostaglandin E2 (PGE2)-induced hyperalgesia by HMWH was attenuated by a TLR4 antagonist (NBP2-26245), but only in male and ovariectomized female rats. ⋯ This treatment completely reversed HMWH-induced anti-hyperalgesia in male rats. Our results demonstrate a sex hormone-dependent, sexually dimorphic involvement of TLR4 in HMWH-induced anti-hyperalgesia, that is MyD88 dependent. PERSPECTIVE: The role of TLR4 in anti-hyperalgesia induced by HMWH is a sexually dimorphic, TLR4 dependent inhibition of inflammatory hyperalgesia that provides a novel molecular target for the treatment of inflammatory pain.
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Review Meta Analysis
Prevalence and interference of chronic pain among people with haemophilia: A systematic review and meta-analysis.
Chronic pain is a common condition among people with hemophilia (PWH), associated with joint deterioration due to repeated joint bleeds. This systematic review and meta-analysis aimed to determine the prevalence of chronic pain due to haemophilia and to analyze its interference in the lives of patients. A systematic search was performed in May and June 2019 and updated in February 2021, using PubMed, EMBASE, Web of Science and SciElo. ⋯ Research in the hemophilia field should clearly distinguish between acute and chronic pain and provide complete characterization of study samples. PERSPECTIVE: Pain is a central issue in the lives of people with hemophilia, posing a significant challenge for healthcare providers. A clear picture of chronic pain due to hemophilia is precluded by high heterogeneity among studies and various definitions used to investigate its prevalence.
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The failure of past practices and policies related to opioid prescribing for chronic pain has led federal agencies and professional organizations to recommend multimodal approaches that prioritize evidence-based nonpharmacological pain treatments (NPTs). These multimodal approaches, which include both traditional and complementary/integrative approaches, hold great promise for reducing the burden of chronic pain and reducing opioid use. ⋯ Despite these dual crises of chronic pain and opioid use in the U. S., there has never been a concerted effort to broadly educate the American public about these issues and NPT pain management options.
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The aims of this longitudinal study were to 1) identify categories of adverse childhood experiences (ACEs) (ie, neglect, abuse, household dysfunction in childhood) that increase risk for internalizing mental health problems, pain-related impairment, and poorer quality of life and 2) examine the moderating role of posttraumatic stress symptoms (PTSS) in these associations, in a clinical sample of youth with chronic pain. At 2 timepoints, youth (N = 155; aged 10-18 years) completed measures of exposure to ACEs, PTSS, depressive and anxiety symptoms, pain intensity, pain interference, and quality of life. Multivariate analyses of variance, linear mixed modeling, and moderation analyses were conducted. ⋯ Findings underscore the influence that ACEs can have on the long-term functioning of youth with chronic pain as well as the important role of current PTSS in this association. PERSPECTIVE: This study found that the risk of poorer outcomes imposed by ACEs at baseline remains longitudinally and that posttraumatic stress symptoms (PTSS) moderate the relationship between ACEs and anxiety and depressive symptoms in youth with chronic pain. These results underscore the importance of assessing for ACEs and PTSS alongside chronic pain in youth.
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Excessive generalization of fear and avoidance are hallmark symptoms of chronic pain disability, yet research focusing on the mechanisms underlying generalization of avoidance specifically, is scarce. Two experiments investigated the boundary conditions of costly pain-related avoidance generalization in healthy participants who learned to avoid pain by performing increasingly effortful (in terms of deviation and force) arm-movements using a robot-arm (acquisition). During generalization, novel, but similar arm-movements, without pain, were tested. ⋯ These results suggest that uncertainty about the occurrence of pain may delay recovery, due to reduced disconfirmation of threat beliefs when exploring, resulting in persistent avoidance. PERSPECTIVE: This article demonstrates generalization of instrumentally acquired costly pain-related avoidance in healthy people under conditions of uncertainty. The results suggest that targeting pain-related uncertainty may be a useful tool for clinicians adopting a psychological approach to treating excessive pain-related avoidance in chronic pain.