UCSF researchers identified estrogen receptor beta (ERβ) as a key driver of chronic visceral pain, with the hormone directly sensitizing nerve pathways in gut tissues. The study used genetic knockout models to demonstrate that ERβ deletion significantly reduced pain responses to intestinal inflammation, while estrogen administration amplified pain sensitivity in both male and female subjects. This mechanistic discovery helps explain why gastrointestinal disorders like irritable bowel syndrome disproportionately affect women, who experience these conditions at nearly twice the rate of men. The finding represents a significant advance in understanding sex-based pain differences, moving beyond correlational observations to identify specific molecular targets. Previous research established that women report more severe and frequent visceral pain, but the underlying biology remained unclear. This ERβ pathway could become a therapeutic target for developing sex-specific treatments for chronic gut disorders. However, the research primarily used animal models, and translating these findings to human therapeutics will require careful consideration of estrogen's broader physiological roles. The work suggests that personalized pain management strategies should account for hormonal status, potentially revolutionizing treatment approaches for millions suffering from chronic abdominal pain conditions.