A link between plasma membrane calcium ATPase 2 (PMCA2), estrogen and estrogen receptor α signaling in mechanical pain

Autor:	Yuan Xiang Tao, Cigdem Acioglu, Ayomi Ratnayake, Lun Li, Li Ni, Stella Elkabes, Veronika Khariv, Robert F. Heary
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Male Pain Threshold 0301 basic medicine Agonist Spinal Cord Dorsal Horn medicine.medical_specialty medicine.drug_class Ovariectomy Analgesic Pain Estrogen receptor lcsh:Medicine Article Gene Knockout Techniques Mice Plasma Membrane Calcium-Transporting ATPases 03 medical and health sciences Basal (phylogenetics) 0302 clinical medicine Internal medicine Threshold of pain medicine Animals lcsh:Science Injections Spinal Sex Characteristics Multidisciplinary Estradiol Chemistry lcsh:R Estrogen Receptor alpha Disease Models Animal 030104 developmental biology Endocrinology Estrogen Plasma membrane Ca2+ ATPase Female lcsh:Q sense organs Orchiectomy Estrogen receptor alpha 030217 neurology & neurosurgery Signal Transduction
Zdroj:	Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Scientific Reports
ISSN:	2045-2322
Popis:	Earlier studies on genetically modified mice indicated that plasma membrane calcium ATPase 2 (PMCA2), a calcium extrusion pump, plays a novel and sex-dependent role in mechanical pain responses: female, but not male, PMCA2+/− mice manifest increased mechanical pain compared to female PMCA2+/+ mice. The goal of the present studies was to determine the contribution of ovarian steroids to the genotype- and sex-dependent manifestation of mechanical pain in PMCA2+/+ versus PMCA2+/− mice. Ovariectomy increased mechanical pain sensitivity and 17β-estradiol (E2) replacement restored it to basal levels in PMCA2+/+ mice, but not in PMCA2+/− littermates. Intrathecal administration of an estrogen receptor alpha (ERα) agonist induced ERα signaling in the dorsal horn (DH) of female PMCA2+/+ mice, but was ineffective in PMCA2+/− mice. In male PMCA2+/+ and PMCA2+/− mice, E2 treatment following orchidectomy did not recapitulate the genotype-dependent differential pain responses observed in females and the agonist did not elicit ERα signaling. These findings establish a novel, female-specific link between PMCA2, ERα and mechanical pain. It is postulated that PMCA2 is essential for adequate ERα signaling in the female DH and that impaired ERα signaling in the female PMCA2+/− mice hinders the analgesic effects of E2 leading to increased sensitivity to mechanical stimuli.
Databáze:	OpenAIRE
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