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Several authors have reported pain prevalence for multiple sites within the same sample and allow a less biased opportunity to compare the magnitude of sex differences across pain sites. A nationwide study of Swedish students in grades 3, 6, and 9 compared the 7-day prevalence of headache, abdominal, and musculoskeletal pain.49 Girls were more than twice as likely as boys to suffer from headaches (17%, 8%). Abdominal pain was experienced weekly by 10% of the girls and 5% of the boys with sex differences significant only in grades 6 and 9. There were no sex differences for musculoskeletal pain, but prevalence increased with age for girls. It provides a platform for users to engage in intimate conversations and explore their sexuality in a safe, private, and controlled environment.

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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.

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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.

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Sex hormones can affect disease pathophysiology, which can affect disease-related pain. For example, the effects of estrogens on bone deposition and cartilage homeostasis could influence the development of articular pathology and pain.400 Of more direct relevance to pain are the hormonal contributions to inflammation. 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. The inflammatory response to various triggering events involves plasma extravasation, chemotactic attraction of leukocytes, and, in turn, stimulated release of inflammatory cytokines and growth factors.

SOX9 is a transcription factor with a DNA-binding site very similar to SRY, and plays a crucial role in the cascade of gene interactions for differentiation and development of the testis3). In 1999, SOX9 overexpression in a 46,XX gonad was identified as leading to an induction of male genitalia in the absence of SRY4). Although there have been a few reports to date of 46,XX SRY-negative patients having duplication of SOX94,5,6,7), SOX9 duplication is not a common cause of 46,XX testicular DSD8). In Korea, less than 10 SRY-positive 46,XX patients have been reported, and there are no reports of 46,XX testicular DSD resulting from SOX9 duplication9). Anime AI uses advanced AI algorithms and generative models to create original anime or manga art based on user inputs.

Using this approach, Hamberg and colleagues177 found that when the neck pain case was a woman, female and male medical students were more likely to provide nonspecific somatic diagnoses, address psychosocial variables in the history, and to prescribe analgesic and psychoactive medications. This review of recent clinical and epidemiologic findings generally indicates that women are at increased risk for many chronic pain conditions, and women tend to report higher levels of acute procedural pain. These sex differences appear smaller (or nonexistent) in children and appear to emerge or increase in magnitude during adolescence. Inevitably, these sex differences in clinical pain are driven by multiple biopsychosocial factors, which will be discussed below. 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.

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.

Two studies reported that sex differences in temporal summation to heat156 and mechanical361 stimulation persisted in clinical pain populations with low back pain and temporomandibular disorders, respectively. Thus, on balance, the evidence supports the conclusion that temporal summation is greater among females than males. A recent meta-analysis on sex differences in osteoarthritis using clinical markers as the case definition (not pain) indicated that females are at significantly increased risk for osteoarthritis (OA) in the knee and hand compared with males.382 Several studies have documented sex differences in pain prevalence, ratings, and depression in OA, and we will review selected studies below. NSFW Character AI represents a groundbreaking advancement in traditional AI chat technology, introducing a nsfw chat bot specifically designed for users to explore their NSFW character fantasies without restraint. This advanced platform not only facilitates a liberating space for expression but also comes equipped with sophisticated character creation tools and an intuitive interface, making it an ideal adult AI companion. As a safer and more appropriate option, platforms explicitly designed to host NSFW content should be sought.

Studies of laboratory pain provide additional evidence of hormonal influences on pain responses. The results from 22 studies that examined sex differences in experimental cold pain are presented in the lower portion of Table 6. Most studies have used some form of the cold pressor test in which subjects immerse their arm or hand in circulating cold water for a defined period of time, and their results support the hypothesis that cold pain sensitivity is more pronounced in females. Sex differences in cold pain were observed in 67% (6/9) of studies reporting cold pain threshold, 93% (14/15) of studies reporting cold pain tolerance, and 81% (13/16) of studies reporting continuous or retrospective subjective pain ratings to cold water immersion.

Combining the data from Table 11 with the studies reviewed by Miaskowski and Levine,277 there is some suggestion that when using PCA women consume lower doses of morphine. 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. Alternatively, one could argue that women benefit more from the increased sense of control that accompanies self-administration of opioids. Additional research will be required to confirm or refute these possibilities.