Local Synthesis of Estradiol in the Rostral Ventromedial Medulla Protects against Widespread Muscle Pain in Male Mice.

Autor:	Plumb AN; Departments of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, 52242., Lesnak JB; Departments of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, 52242., Kolling LJ; Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, 52242., Marcinkiewcz CA; Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, 52242., Sluka KA; Departments of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, 52242 kathleen-sluka@uiowa.edu.; Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, 52242.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2024 Aug 28; Vol. 11 (8). Date of Electronic Publication: 2024 Aug 28 (Print Publication: 2024).
DOI:	10.1523/ENEURO.0332-24.2024
Abstrakt:	Animal studies consistently demonstrate that testosterone is protective against pain in multiple models, including an animal model of activity-induced muscle pain. In this model, females develop widespread muscle hyperalgesia, and reducing testosterone levels in males results in widespread muscle hyperalgesia. Widespread pain is believed to be mediated by changes in the central nervous system, including the rostral ventromedial medulla (RVM). The enzyme that converts testosterone to estradiol, aromatase, is highly expressed in the RVM. Therefore, we hypothesized that testosterone is converted by aromatase to estradiol locally in the RVM to prevent development of widespread muscle hyperalgesia in male mice. This was tested through pharmacological inhibition of estrogen receptors (ERs), aromatase, or ER-α in the RVM which resulted in contralateral hyperalgesia in male mice (C57BL/6J). ER inhibition in the RVM had no effect on hyperalgesia in female mice. As prior studies show modulation of estradiol signaling alters GABA receptor and transporter expression, we examined if removal of testosterone in males would decrease mRNA expression of GABA receptor subunits and vesicular GABA transporter (VGAT). However, there were no differences in mRNA expression of GABA receptor subunits of VGAT between gonadectomized and sham control males. Lastly, we used RNAscope to determine expression of ER-α in the RVM and show expression in inhibitory (VGAT+), serotonergic (tryptophan hydroxylase 2+), and μ-opioid receptor expressing (MOR+) cells. In conclusion, testosterone protects males from development of widespread hyperalgesia through aromatization to estradiol and activation of ER-α which is widely expressed in multiple cell types in the RVM. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 Plumb et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu