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.