Reduced GABA(A) receptor 6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity.
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Trigeminal ganglia neurons express the GABA(A) receptor subunit alpha 6 (Gabr6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabr6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabr6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabr6 gene (Gabr6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund's adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabr6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabr6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabr6 siRNA infusion reduced Gabr6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabr6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabr6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception.
author list (cited authors)
Puri, J., Vinothini, P., Reuben, J., Bellinger, L. L., Ailing, L., Peng, Y. B., & Kramer, P. R.
complete list of authors
Puri, J||Vinothini, P||Reuben, J||Bellinger, LL||Ailing, L||Peng, YB||Kramer, PR