Estrogen in Cycling Rats Alters Gene Expression in the Temporomandibular Joint, Trigeminal Ganglia and Trigeminal Subnucleus Caudalis/Upper Cervical Cord Junction

Females report temporomandibular joint (TMJ) pain more than men and studies suggest estrogen modulates this pain response. Our goal in this study was to determine genes that are modulated by physiological levels of 17 beta-estradiol that could have a role in TMJ pain. To complete this goal, saline or complete Freund's adjuvant was injected in the TMJ when plasma 17 beta-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion, and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C1-2) tissues were isolated from the treated rats and expression of 184 genes was quantitated in each tissue using real-time PCR. Significant changes in the amount of specific transcripts were observed in the TMJ tissues, trigeminal ganglia, and Vc/C1-2 region when comparing rats with high and low estrogen. GABA A receptor subunit alpha 6 (Gabra6) and the glycine receptor alpha 2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a >29-fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabr alpha 6 and Glr alpha 2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors alpha and beta are present in neurons of the trigeminal ganglia, whereby 17 beta-estradiol can alter expression of Gabr alpha 6 and Glr alpha 2. Also, estrogen receptor alpha (ER alpha) but not ER beta was observed in satellite glial cells of the trigeminal ganglia. These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17b-estradiol. J. Cell. Physiol. 226: 3169-3180, 2011. (C) 2011 Wiley Periodicals, Inc.