The Clinical journal of pain
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Sex differences in the response threshold to painful stimuli and the higher number of chronic pain syndromes in women than in men have prompted a series of studies on lower animals and humans aimed at clarifying the role of gonadal hormones in pain. ⋯ This article examines the morphologic and functional aspects of gonadal hormone systems and the relations between gonadal hormones and pain circuits, to identify areas deserving of increased attention in elucidating the endocrine mechanisms that contribute to abnormal pain states.
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Numerous experimental studies, conducted primarily over the past 10 years, show that there are sex differences in opioid analgesia. This review summarizes the published literature on sex differences in analgesia produced by acute administration of drugs acting at mu-, kappa-, and delta-opioid receptors, in animals and humans. Additionally, methodological issues in research into opioid sex differences are discussed. ⋯ Procedural variables that may influence the outcome of studies examining sex differences in opioid analgesia include modality and intensity of the noxious stimulus used in the pain test, opioid type (efficacy and selectivity), and experimental design and data analytic techniques. Subject variables that may be important to consider include subject genotype and gonadal steroid hormone state of the subject at the time of analgesia testing. Evidence is provided for multiple mechanisms underlying sex differences in opioid analgesia, including both pharmacokinetic and pharmacodynamic factors. Future research directions are suggested, such as examining sex differences in opioid tolerance development, sex differences in opioid analgesia using models of acute inflammatory pain and chronic pain, and sex differences in effects of opioids other than analgesia, which may limit their therapeutic use.
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Analgesic drug development as currently undertaken is limited by a number of factors that contribute to the paucity of new analgesics introduced into clinical practice despite marked advances in delineating of the molecular-genetic mechanisms contributing to acute and chronic pain. The participants in this workshop explored the unmet need in analgesia and recommended strategies for enhancing analgesic drug development in the future. The workshop concluded that translating scientific advances into improved pain relief will require new thinking and a cooperative effort among the pharmaceutical industry, regulatory agencies, funding agencies, the biomedical research community, professional societies and clinicians. The workshop also recommended that a better understanding of the epidemiology of pain could contribute to improvement in clinical trial methodology and outcome measures.
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The treatment of pain during pregnancy other than that of labor is a clinical issue that has not been addressed in a systematic manner. ⋯ Experience in women seeking recovery from opioids and their newborns illustrates that opioids are an effective and safe pharmacological option for the treatment of pain during pregnancy. Controlled studies are needed to expand knowledge in this clinical area.