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Several studies have addressed whether physical or psychological interventions differentially influence pain responses in men versus women, and these studies are summarized in the lower portion of Table 10. The majority of these studies (5/6, 81%) indicate that females exhibit more efficient pain inhibitory responses compared with males. For example, using an isometric handgrip exercise, pressure pain threshold was elevated in females but not males, suggesting that exercise-induced analgesia was greater in females.226 However, sex-related differences in pain modulation may be dependent on the type of stressor and pain modality. For example, in response to a laboratory public-speaking stressor, males exhibited a greater stress-related reduction in heat pain, whereas females showed a greater reduction with ischemic pain.45 Sternberg et al387 reported that cold pain was reduced in males during video game competition, whereas pain was more substantially reduced by physical exercise in females.

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Although this has been noted in previous reviews,127,327 a substantial increase in the number of studies has occurred, some of which have used more clinically relevant experimental pain models. For example, findings indicate that women show more robust temporal summation of pain and experience higher levels of pain after intramuscular injection of algesic substances, such as glutamate and hypertonic saline. Also, only recently has evidence emerged indicating that men may exhibit greater DNIC than women, and recent findings suggest that DNIC may be particularly predictive of clinical pain.101,108,453 Additional data regarding sex differences in responses to analgesic medications have been quite mixed and general conclusions are difficult to draw. We have also discussed multiple “biological” and “psychosocial” mechanisms that may contribute to sex differences in pain and analgesic responses, including gonadal hormones, endogenous pain modulatory systems, gender roles, and cognitive/affective factors. Sex-related influences on pain and analgesia have become a topic of tremendous scientific and clinical interest, especially in the last 10 to 15 years. Members of our research group published reviews of this literature more than a decade ago, and the intervening time period has witnessed robust growth in research regarding sex, gender, and pain.

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Overall, each study reported sex differences in at least one pain outcome, but, similar to heat pain, discrepancies among pain outcomes occur between indices of cold pain within studies. For example, Jones et al205 observed sex-related differences for cold pain tolerance but not threshold. Based on the present set of studies, it appears that sex differences in cold pain are consistent, particularly for suprathreshold measures such as tolerance and pain ratings.