Activation of estrogen receptor α enhances bradykinin signaling in peripheral sensory neurons of female rats.
Numerous studies have demonstrated that females have a higher risk of experiencing several pain disorders with either greater frequency or severity than males. Although the mechanisms that underlie this sex disparity remain unclear, several studies have shown an important role for sex steroids, such as estrogen, in the modulation of nociception. Receptors for estrogen are present in primary afferent neurons in the trigeminal and dorsal root ganglia, and brief exposure to estrogen increases responses to the inflammatory mediator bradykinin (BK). However, the mechanism for estrogen-mediated enhancement of BK signaling is not fully understood. The aim of the present study was to evaluate the relative contributions of estrogen receptor α (ERα), ERβ, and G protein-coupled estrogen receptor 1 (GPER) to the enhanced signaling of the inflammatory mediator BK by 17β-estradiol (17β-E2) in primary sensory neurons from female rats in culture (ex vivo) and in behavioral assays of nociception in vivo. The effects of 17β-E2 on BK responses were mimicked by ERα-selective agonists and blocked by ERα-selective antagonists and by small interfering RNA knockdown of ERα. The data indicate that ERα is required for 17β-E2-mediated enhancement of BK signaling in peripheral sensory neurons in female rats.
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Matthew P
MP
Rowan
Kelly A
KA
Berg
James L
JL
Roberts
Kenneth M
KM
Hargreaves
William P
WP
Clarke
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D047628:Estrogen Receptor alpha; D004958:Estradiol; D001920:Bradykinin