Sex-specific mechanisms of chronic pain

For decades, we have known that women, especially younger women, are disproportionately affected by pain disorders, including irritable bowel syndrome, endometriosis, menstrual migraines, fibromyalgia, osteoarthritis, and neuropathic pain, all of which degrade quality of life. The adoption of sex as a biological variable in 2016 has begun to transform the field, revealing distinct sex-specific pathways that initiate, amplify, and resolve pain. In this Review, we synthesize recent advances across visceral and somatic pain, highlighting the impact of sex hormones, immune-neural cross-talk, the gut microbiome, and endogenous analgesic circuits. Rather than clinging to the historical standard that simply described the female bias in pain symptoms, these studies begin to explain why females experience heightened pain, paving the path for mechanism-based precision therapeutics.