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Two studies reported that males displayed higher pain threshold and tolerance.128,161 Despite large sample sizes for several studies,107,124,132,133,161 sex differences in ischemic pain have not been statistically significance due to their small effect sizes. Epidemiologic studies of pain typically report point prevalence (currently in pain), period prevalence (ie, experiencing pain during the past month or year), or lifetime prevalence. Some of the studies reviewed have measured pain intensity or severity ratings and depression, a common impact of chronic pain, and when sex differences were tested, we will report the findings. One issue worth mentioning is over interpretation of positive findings for sex differences in pain due to publication biases. It seems plausible that in some cases sex differences were tested, found to be nonsignificant, and then not reported in a manuscript.93 This may be particularly true for population-based studies of prevalence in which pain intensity or severity is of secondary interest.
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- One issue worth mentioning is over interpretation of positive findings for sex differences in pain due to publication biases.
- The parents provided formal informed consent to permit peripheral blood sampling for genetic testing, and the Institutional Review Board of Seoul National University Hospital approved this study.
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- We have previously suggested that sex differences in nociceptive processing, which would be manifested in responses to experimentally induced pain, represent one potentially important contributing factor.
- Studies from Finland,322,352 Germany,159 Sweden,267 Turkey,309 the United States,326 Nigeria,302 and Brazil25 have drawn similar conclusions for tooth pain, jaw joint pain, and other orofacial pain conditions.
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Recently, questionnaires have been developed based on the analysis of the characteristics of pain (ie, pain descriptors) that discriminate pain due to a definite neurological lesion. Torrance et al409 estimated the prevalence of pain of predominantly neuropathic origin using a random sample of 6000 adults from family practices in three United Kingdom cities using a 5-item neuropathic pain scale developed by Bennett.28 Females (6%) showed greater prevalence of neuropathic pain (lasting longer than 3 months) compared with males (3%). Using a large representative sample of the French population, Bouhassira et al44 assessed neuropathic pain using their symptom-based screen for pain with neuropathic qualities43 and found higher 3-month prevalence in females (8%) compared with males (6%). Neither study reported sex differences in the effects of age, pain intensity, or depression.
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To complete the translational continuum, it is important to determine whether sex-related genetic associations such as these discovered in the laboratory setting will extend to clinical populations. Human brain imaging represents another methodology that holds promise for facilitating mechanistic and translational advancements, and increased application of imaging to enhance understanding of sex differences in pain and analgesia is strongly recommended. Since our two previous reviews127,327 a large number of studies using widely varying methodologies have investigated sex differences in experimental pain sensitivity. Based on the overall findings, it can be concluded that females are more sensitive to painful stimulation as assessed in the laboratory. From the pattern of results, it is difficult to pinpoint any specific mechanism(s), because the sex differences appear relatively consistently across multiple stimulus modalities. However, the recently developed literature on pain in response to intramuscular injections of algesic substances reveals robust and unanimous differences, suggesting that deep, tonic stimuli that mimic clinical musculoskeletal pain may be particularly sensitive to sex differences.
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