Abstract
Numerous studies have reported a greater incidence of symptomatic TMJ inflammation/pain in females suggesting gonadal hormones may play a role. Previous studies in our lab showed expression of the GABAA receptor subunit α6 (Gabrα6) was significantly upregulated in the trigeminal ganglion (TG) neurons when comparing rats given high (proestrus) versus low (diestrus) concentrations of estrogen suggesting involvement of the Gabrα6 subunit in TMJ nociception. This increase in Gabrα6 expression was observed in rats with and without TMJ inflammation. The aim of this study was to determine if siRNA knock-down of Gabrα6 expression in the TG affects TMJ nociception. To address this aim, the TG of male Sprague-Dawley rats was bilaterally cannulated and infused with Gabrα6 siRNA, control siRNA or saline. Two days later the rats received bilateral TMJ injection (15 μg) of complete Freund's adjuvant or saline. A behavioral change (i.e. meal duration), phosphorylated ERK (p-ERK) expression in neurons and glia of the TG was used to determine nociception in rats with TMJ inflammation. p-ERK levels and single cell recordings of cells (± 1mM TMJ ATP injection) in the TG and the lamina I/II layers of C1 were completed to assess non-inflammatory TMJ nociception. The results show Gabrα6 siRNA reduced expression in the TG neurons. In the Gabrα6 siRNA/CFA group, meal duration was significantly longer and p-ERK expression was significantly greater as compared to all other CFA injected groups after 48 hours. In the rats without TMJ inflammation, Gabrα6 siRNA resulted in greater p-ERK expression in TG and increased neuronal activity (spikes/s) in the TG and C1 region as compared to rats infused with control siRNA. In conclusion, reduced expression of Gabrα6 increased the nociceptive response consistent with the idea that Gabrα6 in the TG functions in inhibition of TMJ nociception. Supported by NIDCR grants DE016059-01 (LLB) and DE15372 (PRK).
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