PMID- 23602886 OWN - NLM STAT- MEDLINE DCOM- 20140219 LR - 20220311 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 245 DP - 2013 Aug 15 TI - Reduced GABAA receptor alpha6 expression in the trigeminal ganglion enhanced myofascial nociceptive response. PG - 1-11 LID - S0306-4522(13)00321-7 [pii] LID - 10.1016/j.neuroscience.2013.04.003 [doi] AB - Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabralpha6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabralpha6 role in myofascial pain we hypothesized that Gabralpha6 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 Gabralpha6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabralpha6 gene (Gabralpha6 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 Gabralpha6 and GABAA receptor contents in the TG and Vc-C1 were determined. Gabralpha6 siRNA infusion reduced Gabralpha6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabralpha6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabralpha6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception. CI - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Kramer, P R AU - Kramer PR AD - Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, United States. pkramer@bcd.tamhsc.edu FAU - Bellinger, L L AU - Bellinger LL LA - eng GR - R01 DE016059/DE/NIDCR NIH HHS/United States GR - R01 DE022129/DE/NIDCR NIH HHS/United States GR - DE022129/DE/NIDCR NIH HHS/United States GR - DE016059/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130418 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Gabra6 protein, rat) RN - 0 (Protein Subunits) RN - 0 (Receptors, GABA-A) SB - IM MH - Animals MH - Facial Pain/*metabolism/pathology MH - *Gene Expression Regulation MH - Male MH - Nociception/*physiology MH - Pain Measurement/methods MH - Protein Subunits/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, GABA-A/*biosynthesis/genetics MH - Trigeminal Ganglion/*metabolism PMC - PMC3740526 MID - NIHMS470337 EDAT- 2013/04/23 06:00 MHDA- 2014/02/20 06:00 PMCR- 2014/08/15 CRDT- 2013/04/23 06:00 PHST- 2012/12/11 00:00 [received] PHST- 2013/04/01 00:00 [revised] PHST- 2013/04/02 00:00 [accepted] PHST- 2013/04/23 06:00 [entrez] PHST- 2013/04/23 06:00 [pubmed] PHST- 2014/02/20 06:00 [medline] PHST- 2014/08/15 00:00 [pmc-release] AID - S0306-4522(13)00321-7 [pii] AID - 10.1016/j.neuroscience.2013.04.003 [doi] PST - ppublish SO - Neuroscience. 2013 Aug 15;245:1-11. doi: 10.1016/j.neuroscience.2013.04.003. Epub 2013 Apr 18.