Reduced GABAA receptor 6 expression in the trigeminal ganglion enhanced myofascial nociceptive response.
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Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabr6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabr6 role in myofascial pain we hypothesized that Gabr6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabr6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabr6 gene (Gabr6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1) was measured by quantitating the amount of phosphorylated extracellular signal-regulated kinase (p-ERK). Total Gabr6 and GABAA receptor contents in the TG and Vc-C1 were determined. Gabr6 siRNA infusion reduced Gabr6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabr6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabr6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception.
author list (cited authors)
Kramer, P. R., & Bellinger, L. L.
complete list of authors
Kramer, PR||Bellinger, LL