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

Autor:	Chen Y; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Moutal A; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Navratilova E; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Kopruszinski C; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Yue X; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Ikegami M; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Chow M; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Kanazawa I; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Bellampalli SS; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Xie J; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Patwardhan A; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Rice K; National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA., Fields H; Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA., Akopian A; University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA., Neugebauer V; Texas Tech University Health Science Center, Lubbock, TX 79430, USA., Dodick D; Mayo Clinic, Scottsdale, AZ 85752, USA., Khanna R; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Porreca F; Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA. frankp@medadmin.arizona.edu.; Mayo Clinic, Scottsdale, AZ 85752, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2020 Feb 05; Vol. 12 (529).
DOI:	10.1126/scitranslmed.aay7550
Abstrakt:	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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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