A new study from the University of Arizona Health Sciences has revealed a promising approach to reduce post-operative pain in women by targeting a stress-related hormone known as prolactin. The findings, published in the journal Proceedings of the National Academy of Sciences, may pave the way for new treatments that lessen the need for opioid painkillers after surgery.
Prolactin is a hormone best known for its role in lactation, but it also influences how women experience pain. Researchers, led by Dr. Frank Porreca, found that stress before surgery increases prolactin levels in women, which in turn activates nerve cells (called nociceptors) that transmit pain signals to the brain.
“Stress from anticipating surgery increases prolactin, which makes the body more sensitive to pain,” said Porreca, research director at the UArizona Health Sciences Comprehensive Center for Pain & Addiction. “We now have a clearer picture of how stress heightens the body’s pain response, especially in women.”
The study used mouse models to test three key ideas: that high prolactin levels worsen post-operative pain, stress raises prolactin and increases pain, and lowering prolactin before surgery can ease pain afterward. All three were confirmed by the research.
- To reduce prolactin levels and pain, the team tested three approaches:
- Gene therapy
- Cabergoline, an FDA-approved drug that blocks prolactin by acting on dopamine receptors
PL 200,019, a new monoclonal antibody developed by the team to block prolactin
All methods proved effective in reducing post-surgical pain in female mice.
Porreca said the results could lead to new strategies to improve recovery for women after surgery. Cabergoline, already approved by the FDA, may soon be tested in clinical trials for this new use. PL 200,019 is still in development but shows strong potential for clinical application.
“If we can reduce the need for opioids after surgery, patients will recover faster and face fewer risks,” Porreca said. “This could also lower the chance of pain becoming chronic.”
The research builds on previous work by Porreca’s team, which showed that pain signaling pathways in men and women differ. In women, prolactin plays a central role in sensitizing pain receptors, while in men, a different hormone, orexin, is involved.
The study was co-authored by researchers from the UArizona College of Medicine – Tucson and several collaborators from Saint Louis University, the Atria Institute of Science and Medicine, Anabios Corporation, and Peptide Logic, which is helping develop the prolactin-blocking antibody.
This discovery offers hope for safer, more effective ways to manage surgical pain in women and reduce reliance on opioids—a critical step in addressing both pain and the ongoing opioid crisis.
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