Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction

Abstract

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 17β-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 17β-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C 1-2 ) 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/ C 1-2 region when comparing rats with high and low estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor α2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a greater than 29 fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabrα6 and Glrα2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors α and β are present in neurons of the trigeminal ganglia, whereby 17β-estradiol can alter expression of Gabrα6 and Glrα2. Also, estrogen receptor α (ERα) but not ERβ 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 17β-estradiol.

The association between temporomandibular disorders and joint hypermobility syndrome: a nationwide population-based study

“…Interestingly, in terms of the severity for TMD, sharper symptoms of TMDs were exhibited in females than in males [25,26]. The exact reasons have not yet been determined; however, given the striking predominance of affected women, previous studies proposed that the results could be partially attributed to hormonal influence, and a rise in estrogen levels may be an important risk factor for the pathogenesis of TMD [25,[27][28][29]. It should be emphasized that TMDs are complex multifactorial disorders.…”

Estrogenic influences in pain processing

“…Prolonged exposure to estradiol in neuronal cultures from DRGs of female rats inhibits activation of the ion channel TRPV1, which is central to nociceptive transmission in the DRG (Xu et al, 2008) and cultured trigeminal ganglion cells from ovariectomized rats exhibit increased sensitivity to capsaicin (Diogenes et al, 2006). The expression of various painrelated peptides in the mouse trigeminal ganglion also varies with the estrous cycle (Puri et al, 2011;Puri et al, 2005). Estradiol modulates the expression of P2X3 receptors, known to be involved in peripheral pain signaling, in the trigeminal and dorsal root ganglia thereby affecting nociceptive transmission in the ovariectomized rat Yu et al, 2011).…”

Infusion of Gabrα6 siRNA into the trigeminal ganglia increased the myogenic orofacial nociceptive response of ovariectomized rats treated with 17β-estradiol

“…Moreover, different concentrations of estradiol during the menstral cycle affect the orofacial pain response (Yu et al). To determine how estradiol could potentially alter orofacial sensitivity, gene expression in the TMJ, trigeminal ganglia (TG) and trigeminal subnucleus caudalis/upper cervical cord region (Vc/C 1-2 ) was analyzed with gene arrays after treating rats with physiological doses of 17 β-estradiol (Puri et al, 2011). A subunit of the GABA A receptor, Gabrα6, was affected by 17 β-estradiol in the TG and Vc-C 1 (Puri et al, 2011).…”

“…To determine how estradiol could potentially alter orofacial sensitivity, gene expression in the TMJ, trigeminal ganglia (TG) and trigeminal subnucleus caudalis/upper cervical cord region (Vc/C 1-2 ) was analyzed with gene arrays after treating rats with physiological doses of 17 β-estradiol (Puri et al, 2011). A subunit of the GABA A receptor, Gabrα6, was affected by 17 β-estradiol in the TG and Vc-C 1 (Puri et al, 2011). In addition, a later study found Gabrα6 positive neurons located in the TG projected to the temporomandibular joint (TMJ) (Puri et al, 2012).…”