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

51 Pages Posted: 13 Jun 2019 Sneak Peek Status: Published

See all articles by Mayur Patil

Mayur Patil

University of Texas at San Antonio - Department of Endodontics

Sergei Belugin

University of Texas at San Antonio - Department of Endodontics

Jennifer Mecklenburg

University of Texas at San Antonio - Department of Endodontics

Andi Wangzhou

University of Texas at Dallas - School of Behavioral and Brain Sciences

Chandler Paige

University of Texas at Dallas - School of Behavioral and Brain Sciences

Priscilla Barba-Escobedo

University of Texas at San Antonio - Department of Endodontics

Jacob Boyd

University of Texas at San Antonio - Department of Endodontics

Vincent Goffin

Universite Paris Descartes

David Grattan

University of Otago

Ulrich Boehm

Saarland University

Gregory Dussor

University of Texas at Dallas - School of Behavioral and Brain Sciences

Theodore Price

University of Texas at Dallas - School of Behavioral and Brain Sciences

Armen Akopian

University of Texas at San Antonio - Department of Endodontics

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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 which regulates dimorphic pain responses. Prolactin (PRL), which is involved in many physiologic functions, induces female-specific hyperalgesia. A PRL receptor (Prlr) antagonist in the hindpaw 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 only found 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: Sensory Neurons, inflammatory pain, Prolactin, sex dimorphism, Translation

Suggested Citation

Patil, Mayur and Belugin, Sergei and Mecklenburg, Jennifer and Wangzhou, Andi and Paige, Chandler and Barba-Escobedo, Priscilla and Boyd, Jacob and Goffin, Vincent and Grattan, David and Boehm, Ulrich and Dussor, Gregory and Price, Theodore and Akopian, Armen, Prolactin Regulates Pain Responses Via a Female-Selective Nociceptor-Specific Mechanism (June 13, 2019). ISCIENCE-D-19-00551. Available at SSRN: https://ssrn.com/abstract=3403333 or http://dx.doi.org/10.2139/ssrn.3403333
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Mayur Patil

University of Texas at San Antonio - Department of Endodontics

United States

Sergei Belugin

University of Texas at San Antonio - Department of Endodontics

United States

Jennifer Mecklenburg

University of Texas at San Antonio - Department of Endodontics

United States

Andi Wangzhou

University of Texas at Dallas - School of Behavioral and Brain Sciences

800 W. Campbell Road
Richardson, TX 75080-3021
United States

Chandler Paige

University of Texas at Dallas - School of Behavioral and Brain Sciences

800 W. Campbell Road
Richardson, TX 75080-3021
United States

Priscilla Barba-Escobedo

University of Texas at San Antonio - Department of Endodontics

United States

Jacob Boyd

University of Texas at San Antonio - Department of Endodontics

United States

Vincent Goffin

Universite Paris Descartes

12, rue de l'Ecole de M├ędecine
Cedex 06
Paris, 75270
France

David Grattan

University of Otago

P.O. Box 56
Dunedin, Otago 9010
New Zealand

Ulrich Boehm

Saarland University

Stadtwald
Saarbrucken, Saarland D-66123
Germany

Gregory Dussor

University of Texas at Dallas - School of Behavioral and Brain Sciences

800 W. Campbell Road
Richardson, TX 75080-3021
United States

Theodore Price

University of Texas at Dallas - School of Behavioral and Brain Sciences

800 W. Campbell Road
Richardson, TX 75080-3021
United States

Armen Akopian (Contact Author)

University of Texas at San Antonio - Department of Endodontics ( email )

United States

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