Study: Blocking stress-linked prolactin surge relieves postoperative pain in women

Editor's Note

Blocking stress-induced prolactin may significantly reduce postoperative pain in women and curb the need for opioids, according to a study led by University of Arizona Health Sciences. News-Medical.Net summarized the findings May 20.

Published in Proceedings of the National Academy of Sciences, the research suggests a path toward sex-specific pain management strategies targeting the hormonal effects of surgical stress. As detailed in the article, the neurohormone prolactin—naturally found at higher levels in females—was shown to increase the excitability of female nociceptors, the nerve cells responsible for transmitting pain. The research team found that pre-operative stress can elevate circulating prolactin, creating a physiological setup for more intense and prolonged pain after surgery.

Normally, prolactin is suppressed by dopamine, but stress interrupts this balance, the outlet reports. Using mouse models, researchers confirmed that elevated prolactin intensifies post-operative pain, that stress can act as a trigger for this mechanism, and that lowering prolactin before surgery can improve pain outcomes.

Three approaches proved effective in reducing post-op pain in female mice: gene therapy, the use of cabergoline (a dopamine receptor agonist already FDA-approved), and PL 200,019, a novel monoclonal antibody still under development. According to the article, cabergoline is expected to enter clinical trials to evaluate its utility as a pre-emptive pain intervention.

The outlet reports that both treatments could potentially prevent acute pain from becoming chronic and reduce reliance on opioids—critical in mitigating side effects such as respiratory depression and addiction risk. Researchers also emphasized that limiting post-surgical opioid use can also improve recovery timelines and hospital discharge rates.

As detailed in the report, this study builds on earlier work by the same researchers that identified sexually dimorphic pain mechanisms—specifically, prolactin’s unique role in female nociceptor sensitization versus orexin in males. The research team includes collaborators from the University of Arizona, Saint Louis University, the Atria Institute, AnaBios, and Peptide Logic, which is developing the anti-prolactin antibody.

A quote from Frank Porreca, PhD, the Cosden Professor of Pain and Addiction Studies at the U of A College of Medicine – Tucson, who led the research team, highlights the potential promise. “Many clinicians will tell you that they can predict which patients will have the worst post-operative pain outcomes based on the level of anxiety and stress that a patient exhibits before a scheduled surgery. And it has been shown that women exhibit greater stress responses. Our study uncovered a link between psychological stress and nociceptor activation through prolactin, which means there are approaches we could use preemptive intervention to improve outcomes in post-operative pain in women."