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As technology evolves, so too do the capabilities of these AI entities, offering a glimpse into the future of human-AI relationships. Additional research has attempted to manipulate other gender-related variables. Fillingim et al119 provided instructions designed to manipulate females’ and males’ perceived ability to tolerate ischemic pain, hypothesizing that enhancing perceived ability would produce greater effects in females, because males report higher perceived ability to tolerate pain at baseline. Surprisingly, the group with the highest pain tolerance was males who had been informed that females tolerate the procedure better. In contrast, Robinson and colleagues333 found that sex differences in cold pain tolerance were nonsignificant when participants were given gender-specific expectations for pain tolerance.

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• In a previous review, Rollman and Lautenbacher341 concluded that women have greater frequency of musculoskeletal pain than men.
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Additional peptides are released from C fibers, and spinal N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide production occur.450 This cascade of events can alter the transduction properties of nociceptors, lowering their activation thresholds, and this peripheral sensitization could ultimately lead to central sensitization. The growing body of evidence that has accumulated in the past 10 to 15 years continues to indicate substantial sex differences in clinical and experimental pain responses, and some evidence suggests that pain treatment responses may differ for women versus men. The results from 3 studies that examined sex differences in perceptual responses to electrical pain are presented in the middle portion of Table 5. Pain threshold and tolerance for electrical stimuli were significantly lower in healthy women compared with men. Even though electrical pain was reported for only 3 studies, it strongly favors the hypothesis that women are more sensitive to this pain modality in comparison to men. These recent findings present a more consistent picture than the 5 studies reviewed by Riley et al,327 who found that electrical stimuli produced inconsistent findings and a moderate effect size for the sex difference.

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46,XX male syndrome was first described in ), and the Chicago consensus renamed of this syndrome as 46,XX testicular DSD in ). Most patients have normal male phenotypes at birth, and are usually diagnosed in late adolescence because of delayed puberty, gynecomastia, or infertility2). Approximately 15% of XX males have hypospadias, cryptorchidism, or more severe genital ambiguity13). All 46,XX males are infertile owing to the absence of the azoospermia factor region in the long arm of the Y chromosome14,15).

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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.

For 2008, the first 6 months was collected and doubled to obtain an annualized estimate. The PubMed search for Sex, Gender, and Pain was completed using the following Boolean combination (Sex differences OR Gender differences) AND Pain. 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. A number of the ads found by the Observer on Craigslist were subsequently removed, apparently after being flagged by users.