Sex Differences In Analgesia Research Articles

Morphine responses and experimental pain: Sex differences in side effects and cardiovascular responses but not analgesia

Sex differences in analgesic responses to μ opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to μ opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to μ opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. Perspective This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Qualitative sex differences in κ-opioid analgesia in mice are dependent on age

The effects of aging on sex differences in analgesia from the κ-opioid agonist, U50,488H (U50), were examined in C57BL/6J mice. U50 analgesia can be blocked by the N-methyl- d-aspartate receptor antagonist, MK-801 (MK), in male rodents and gonadectomized females, but not hormonally intact or estrogen-replaced females, suggesting the existence of alternate neurochemical mediation in females. We now report that MK antagonism of U50 analgesia is age-dependent in females. That is, reproductively senescent females display MK-sensitive U50 analgesia qualitatively similar to that displayed by males or hormonally deprived young females. Age-related reductions in U50 analgesic magnitude were also observed in females. Thus, age and gender are likely to alter the clinical efficacy of analgesic drugs active at κ-opioid receptors.

Sex differences in opioid analgesia: clinical and experimental findings

Sex differences in analgesic responses to opioids have received increasing attention in recent years. This article examines the literature on sex differences in opioid analgesia, including the results of studies from the authors' own laboratories. In general, nonhuman animal studies suggest more robust opioid analgesic responses in males relative to females; however, the human studies completed to date seem to indicate greater opioid analgesia among females. The most consistent evidence of sex differences in analgesia comes from studies of κ-agonist-antagonists administered to patients following oral surgery. These data indicate more robust analgesia in females, and dose-response characteristics suggest that these agents possess both analgesic and antianalgesic properties, and the agonists may produce these effects in different proportions for women versus men. In contrast, the data from laboratory pain models in humans suggest greater analgesic effects in women in response μ-opioid agonists but not κ-agonist-antagonists. Multiple mechanisms may explain sex differences in opioid analgesia, including gonadal hormonal effects, pharmacokinetics and pharmacodynamics, genetic influences, balance of analgesic/antianalgesic processes, and psychological factors. However, the disparity of results obtained from different pain models – animals versus humans and clinical pain versus experimental pain in humans – suggests that the models themselves are mechanistically different. Additional investigation is warranted in order to further explicate the nature of sex differences in opioid analgesia and to elucidate the underlying mechanisms.

Sex Differences in Opioid Analgesia: “From Mouse to Man”

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.

Sex differences in drug- and non-drug-induced analgesia

Historically, biomedical research has been conducted almost exclusively with male subjects. A growing number of studies now demonstrate sex differences in analgesia produced both by drugs and by environmental stimuli. This review summarizes the current literature on sex differences in analgesia produced by opioids, cholinergics and other drugs, and by stress, exercise and other environmental manipulations. A brief overview of the physiological mechanisms underlying sex differences in analgesia is provided, as well as suggestions for future research. It is not yet known whether the development of sex-specific analgesia treatment guidelines is warranted.

Sex differences in analgesic responses: evidence from experimental pain models.

Sex-related influences on the experience of pain have received considerable empirical attention. Women are at greater risk for several forms of clinical pain and exhibit greater perceptual responses to experimental pain. In recent years, investigators have turned their attention to the influence of sex-related factors on analgesic responses. The purpose of this review is to examine the literature on sex differences in analgesic responses, emphasizing findings from experimental studies. First, important methodological issues in laboratory pain research are presented, and sex differences in responses to experimentally-induced pain are briefly addressed. Next, previous data from non-human animal research and human experimental and clinical research related to sex differences in analgesia are discussed. Also, preliminary results are presented from an ongoing study in our laboratory examining analgesic responses in women and men. Both previous research and preliminary findings from our laboratory suggests that opioids produce greater analgesic responses in women than men. Potential mechanisms underlying sex differences in analgesia are proposed, and important directions for future research are suggested.

Gender differences in opioid-mediated analgesia: animal and human studies.

Gender differences in opioid-mediated analgesia: animal and human studies.

Sex Differences in Analgesia from Intrathecal Neostigmine in Humans

Sex Differences in Analgesia from Intrathecal Neostigmine in Humans