title: 17-Beta-estradiol enhanced allodynia of inflammatory temporomandibular joint through upregulation of hippocampal TRPV1 in ovariectomized rats.
abstract: Temporomandibular disorders (TMDs) predominantly affect reproductive female patients, with pain the most frequent complaint. Although estrogens are believed to play important roles in TMD pain, the mechanism underlying modulation of TMD pain by estrogens remains largely unknown. Accumulating evidence implies that the hippocampus is involved in sexual dimorphism of pain sensitivity. In this study, we investigated the hippocampal TRPV1 (transient receptor potential vanilloid 1) expression in ovariectomized rats that received 17-beta-estradiol substitution and found that 17-beta-estradiol enhanced the mechanical allodynia of inflamed temporomandibular joint (TMJ) induced by complete Freund's adjuvant. Real-time PCR and immunoblotting demonstrated that TMJ inflammation significantly induced hippocampal TRPV1 expression compared with the control group but failed to induce it in the ovariectomized rats that received no estradiol replacement. In addition, estradiol potentiated TMJ inflammation-induced hippocampal TRPV1 expression in a dose-dependent manner in the ovariectomized rats. In contrast, TRPV1 transcription in amygdala, prefrontal cortex, and thalamus was not affected by TMJ inflammation and estradiol. Immunostaining showed TRPV1 localized in the processes and cytoplasm of pyramidal neurons in CA1-CA3 regions of the hippocampus. Moreover, intrahippocampal injection of TRPV1 antagonists capsazepine and 5'-iodo-resiniferatoxin into the CA1 region of the hippocampus significantly attenuated allodynia of inflamed TMJ in both nonovariectomized and ovariectomized rats that received estradiol replacement. Our results suggested that hippocampal TRPV1 can modulate central pain processing and estradiol may contribute to the sexual dimorphism of TMD pain sensitivity through upregulation of TRPV1 expression in the hippocampus.
authors.affiliation: Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Wu
authors.forename: Ye-Ping
authors.initials: YP
authors.lastname: Bi
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Kou
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Ma
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Wang
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
authors.forename: Xu-Chen
authors.initials: XC
authors.lastname: Ma
mesh_terms: D000818:Animals; D001321:Autistic Disorder; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005620:Freund's Adjuvant; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D010812:Physical Stimulation; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000378:metabolism*; D013705:Temporomandibular Joint Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D004958:Estradiol; D005620:Freund's Adjuvant