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A prolactin-targeting antibody to prevent stress-induced peripheral nociceptor sensitization and female postoperative pain

  • 0Department of Pharmacology, University of Arizona, Tucson, AZ 85724.
Proceedings of the National Academy of Sciences of the United States of America +

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May 12, 2025

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May 12, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Stress amplifies postoperative pain, particularly in women, by sensitizing nerve cells. A new antibody targeting prolactin (PRL) shows promise in preventing this stress-induced pain hypersensitivity in females.

Area Of Science

  • Neuroscience
  • Pain Research
  • Endocrinology

Background

  • Preoperative stress and anxiety are risk factors for prolonged postoperative pain, especially in women.
  • The underlying mechanisms linking psychological stress to heightened postoperative pain in females are not fully understood.
  • Prolactin (PRL), a neurohormone influenced by stress and estrogen, plays a role in nociception.

Purpose Of The Study

  • To investigate the hypothesis that stress sensitizes dorsal root ganglion (DRG) nociceptors, thereby amplifying postoperative pain.
  • To explore the role of prolactin and its receptor isoforms (PRLR-L and PRLR-S) in stress-induced pain hypersensitivity.
  • To evaluate the therapeutic potential of targeting prolactin for managing postoperative pain in females.

Main Methods

  • Utilized restraint stress (RS) and incisional injury models in male and female mice.
  • Investigated the effects of stress and injury on PRLR-L and PRLR-S expression and nociceptor excitability.
  • Employed pharmacological inhibition of pituitary PRL, genetic manipulation (PRLR-L overexpression, CRISPR/Cas9 editing), and a monoclonal antibody (PL200,019) against human PRL (hPRL).
  • Tested PL200,019 in human female nociceptors and in female mice expressing hPRL.

Main Results

  • Restraint stress exacerbated incisional injury-induced pain hypersensitivity in both sexes, with a more pronounced effect in females.
  • In females, stress and injury led to decreased PRLR-L and increased PRL-dependent nociceptor excitability.
  • Pharmacological and genetic interventions targeting PRL signaling selectively inhibited postoperative pain hypersensitivity in females.
  • The anti-PRL antibody PL200,019 effectively blocked hPRL-induced sensitization of human female nociceptors and prevented hypersensitivity in hPRL-expressing mice.

Conclusions

  • Stress-induced sensitization of DRG nociceptors, mediated by prolactin signaling through PRLR-S, is a key mechanism for amplified postoperative pain in females.
  • Targeting prolactin with a monoclonal antibody offers a potential strategy to preemptively inhibit stress-induced nociceptor sensitization.
  • This approach could improve postoperative pain management in women, reduce opioid reliance, and mitigate the risk of chronic pain development.

Keywords:

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