First, without compelling scientific justification limited research to one sex or the other, both preclinical and human studies should routinely include subjects of both sexes. The NIH requires this for human studies; however, nonhuman pain research continues to eschew females.32,283 Given that the clinical pain conditions to which preclinical research is intended to apply are female-predominant, one could argue that preclinical research that excludes females is incomplete at best and invalid at worst. Moreover, clinical studies, which typically include participants of both sexes, should consistently analyze for sex differences and report the findings, whether positive or negative. This would help overcome publication biases, which could overestimate sex differences based on the reduced likelihood of reporting negative findings. Another important conceptual and analytical concern is the distinction between qualitative and quantitative sex differences.
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The prevalence increased with age for both sexes with greater increases for girls. The epidemiology of chronic pain in children has been reviewed by McGrath,272 but differences between boys and girls were only briefly discussed. We will review several large studies that compared the prevalence of headaches, musculoskeletal pain, and abdominal pain in children and adolescents. Another issue concerns geographic or cultural characteristics of the reference population.
Sex hormones may influence multiple central nervous system pathways, including effects on the functioning of endogenous opioid systems, dopaminergic function, serotonergic activity, and other endogenous components involved in the nociceptive processing, as discussed below. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5Ξ±-dihydrotestosterone (5Ξ±-DHT) by the cytoplasmic enzyme 5Ξ±-reductase. 5Ξ±-DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T.[147] The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA.
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- In general, women show a heightened inflammatory response compared with men.394 Although beneficial for wound healing and response to infection, this more robust inflammatory response places women at significantly greater risk for a variety of painful inflammatory autoimmune conditions, including rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus.
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- Consequently, it appears that women are at greater risk for neuropathic pain than men.
- The mechanisms and practical importance of these sex differences merit further investigation in future studies.
- Interestingly, the two studies showing lower morphine requirements for men involved provider administered morphine.16,62 It is tempting to speculate that men may be less willing to report pain or request analgesics from a provider, which would explain their lower opioid consumption in the provider-administered settings.
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