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Papers of the Week

Papers: 1 Feb 2020 - 7 Feb 2020

Animal Studies

2020 02 05

Sci Transl Med



Editor's Pick

The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females.


Chen Y, Moutal A, Navratilova E, Kopruszinski C, Yue X, Ikegami M, Chow M, Kanazawa I, Bellampalli S S, Xie J, Patwardhan A, Rice K, Fields H, Akopian A, Neugebauer V, Dodick D, Khanna R, Porreca F
Sci Transl Med. 2020 02 05; 12(529).
PMID: 32024801.


Pain is more prevalent in women for reasons that remain unclear. We have identified a mechanism of injury-free nociceptor sensitization and opioid-induced hyperalgesia (OIH) promoted by prolactin (PRL) in females. PRL signals through mutually inhibitory long (PRLR-L) and short (PRLR-S) receptor isoforms, and PRLR-S activation induces neuronal excitability. PRL and PRLR expression were higher in females. CRISPR-mediated editing of PRLR-L promoted nociceptor sensitization and allodynia in naïve, uninjured female mice that depended on circulating PRL. Opioids, but not trauma-induced nerve injury, decreased PRLR-L promoting OIH through activation of PRLR-S in female mice. Deletion of both PRLR-L and PRLR-S (total PRLR) prevented, whereas PRLR-L overexpression rescued established OIH selectively in females. Inhibition of circulating PRL with cabergoline, a dopamine D2 agonist, up-regulated PRLR-L and prevented OIH only in females. The PRLR-L isoform therefore confers protection against PRL-promoted pain in females. Limiting PRL/PRLR-S signaling pharmacologically or with gene therapies targeting the PRLR may be effective for reducing pain in a female-selective manner.