Can new understanding of sexually dimorphic pain mechanisms provide a path to improved postoperative pain outcomes in women?

Pain. 2026 Mar 25. doi: 10.1097/j.pain.0000000000003966. Online ahead of print.

ABSTRACT

Preoperative stress is a known predictor of worsened postoperative pain. Women have higher stress responses and greater and longer-lasting postoperative pain than men. We suggest that prolonged anticipatory stress during the period before scheduled surgeries can lead to a long-lasting remodeling of nociceptors in women, increasing their sensitivity to noxious and normally innocuous stimuli and consequently worsening postoperative pain in women. The mechanism underlying remodeling of nociceptors in women may involve prolactin, a pituitary neurohormone released into the circulation by stress, and subsequent dysregulation of expression of prolactin receptor isoforms. We propose that the link between pituitary prolactin and nociceptor sensitization provides an opportunity for preoperative intervention to reduce postoperative pain in women. Short-term administration of dopamine D2 receptor agonists to inhibit stress-induced release of pituitary prolactin in the period before scheduled surgery may prevent nociceptor sensitization before the surgical injury. Potential benefits could include reduced postoperative pain, diminished need for postoperative opioids and their associated side-effects, speeding time to recovery and decreased risk of development of chronic postoperative pain. Monoclonal antibodies preventing prolactin signaling are in development and may also become available to improve postoperative pain in women.

PMID:41875281 | DOI:10.1097/j.pain.0000000000003966