Prolactin Regulates Pain Responses via a Female-Selective Nociceptor-Specific Mechanism

Mayur Patil; Sergei Belugin; Jennifer Mecklenburg; Andi Wangzhou; Candler Paige; Priscilla A Barba-Escobedo; Jacob T Boyd; Vincent Goffin; David Grattan; Ulrich Boehm; Gregory Dussor; Theodore J Price; Armen N Akopian

doi:10.1016/j.isci.2019.09.039

Prolactin Regulates Pain Responses via a Female-Selective Nociceptor-Specific Mechanism

iScience. 2019 Oct 25:20:449-465. doi: 10.1016/j.isci.2019.09.039. Epub 2019 Oct 1.

Authors

Affiliations

¹ Department of Endodontics, The School of Dentistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Molecular Pharmacology and Physiology, University South Florida (USF), Tampa, FL 33612, USA.
² Department of Endodontics, The School of Dentistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
³ School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
⁴ Department of Endodontics, The School of Dentistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
⁵ Inserm U1151, Université Paris Descartes, Paris, France.
⁶ Centre for Neuroendocrinology and Department of Anatomy, University of Otago School of Biomedical Sciences, Dunedin, New Zealand.
⁷ Department of Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.
⁸ School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA. Electronic address: theodore.price@utdallas.edu.
⁹ Department of Endodontics, The School of Dentistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: akopian@uthscsa.edu.

Abstract

Many clinical and preclinical studies report an increased prevalence and severity of chronic pain among females. Here, we identify a sex-hormone-controlled target and mechanism that regulates dimorphic pain responses. Prolactin (PRL), which is involved in many physiologic functions, induces female-specific hyperalgesia. A PRL receptor (Prlr) antagonist in the hind paw or spinal cord substantially reduced hyperalgesia in inflammatory models. This effect was mimicked by sensory neuronal ablation of Prlr. Although Prlr mRNA is expressed equally in female and male peptidergic nociceptors and central terminals, Prlr protein was found only in females and PRL-induced excitability was detected only in female DRG neurons. PRL-induced excitability was reproduced in male Prlr⁺ neurons after prolonged treatment with estradiol but was prevented with addition of a translation inhibitor. We propose a novel mechanism for female-selective regulation of pain responses, which is mediated by Prlr signaling in sensory neurons via sex-dependent control of Prlr mRNA translation.

Keywords: Female Reproductive Endocrinology; Sensory Neuroscience.

Abstract

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