PMID- 23740773 OWN - NLM STAT- MEDLINE DCOM- 20140728 LR - 20211021 IS - 1532-2149 (Electronic) IS - 1090-3801 (Print) IS - 1090-3801 (Linking) VI - 18 IP - 1 DP - 2014 Jan TI - Peripheral G protein-coupled inwardly rectifying potassium channels are involved in delta-opioid receptor-mediated anti-hyperalgesia in rat masseter muscle. PG - 29-38 LID - 10.1002/j.1532-2149.2013.00343.x [doi] AB - BACKGROUND: Although the efficacy of peripherally administered opioid has been demonstrated in preclinical and clinical studies, the underlying mechanisms of its anti-hyperalgesic effects are poorly understood. G protein-coupled inwardly rectifying potassium (GIRK) channels are linked to opioid receptors in the brain. However, the role of peripheral GIRK channels in analgesia induced by peripherally administered opioid, especially in trigeminal system, is not clear. METHODS: Expression of GIRK subunits in rat trigeminal ganglia (TG) was examined with reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. Chemical profiles of GIRK-expressing neurons in TG were further characterized. Behavioural and Fos experiments were performed to examine the functional involvement of GIRK channels in delta-opioid receptor (DOR)-mediated anti-hyperalgesia under an acute myositis condition. RESULTS: TG expressed mRNA and proteins for GIRK1 and GIRK2 subunits. Majority of GIRK1- and GIRK2-expressing neurons were non-peptidergic afferents. Inhibition of peripheral GIRK using Tertiapin-Q (TPQ) attenuated antinociceptive effects of peripherally administered DOR agonist, [D-Pen(2), D-Pen(6) ]-enkephalin (DPDPE), on mechanical hypersensitivity in masseter muscle. Furthermore, TPQ attenuated the suppressive effects of peripheral DPDPE on neuronal activation in the subnucleus caudalis of the trigeminal nucleus (Vc) following masseteric injection of capsaicin. CONCLUSIONS: Our data indicate that peripheral DOR agonist-induced suppression of mechanical hypersensitivity in the masseter muscle involves the activity of peripheral GIRK channels. These results could provide a rationale for developing a novel therapeutic approach using peripheral GIRK channel openers to mimic or supplement the effects of peripheral opioid agonist. CI - (c) 2013 European Pain Federation - EFIC(R) FAU - Chung, M-K AU - Chung MK AD - Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, USA. FAU - Cho, Y S AU - Cho YS FAU - Bae, Y C AU - Bae YC FAU - Lee, J AU - Lee J FAU - Zhang, X AU - Zhang X FAU - Ro, J Y AU - Ro JY LA - eng GR - R01 DE016062/DE/NIDCR NIH HHS/United States GR - R01 DE019448/DE/NIDCR NIH HHS/United States GR - DE019448/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130606 PL - England TA - Eur J Pain JT - European journal of pain (London, England) JID - 9801774 RN - 0 (Analgesics, Opioid) RN - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels) RN - 0 (Kcnj6 protein, rat) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Opioid, delta) RN - 0 (Sensory System Agents) RN - 88373-73-3 (Enkephalin, D-Penicillamine (2,5)-) RN - S07O44R1ZM (Capsaicin) SB - IM MH - Analgesics, Opioid/pharmacology MH - Animals MH - Behavior, Animal/physiology MH - Blotting, Western MH - Brain Stem/cytology/drug effects MH - Capsaicin/pharmacology MH - Enkephalin, D-Penicillamine (2,5)-/pharmacology MH - G Protein-Coupled Inwardly-Rectifying Potassium Channels/drug effects/*physiology MH - Genes, fos MH - Hyperalgesia/*physiopathology MH - Immunohistochemistry MH - Male MH - Masseter Muscle/*physiopathology MH - Physical Stimulation MH - RNA, Messenger/biosynthesis/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Receptors, Opioid, delta/*physiology MH - Sensory System Agents/pharmacology MH - Trigeminal Ganglion/cytology/drug effects/physiology PMC - PMC4153343 MID - NIHMS516366 COIS- Conflict of interest: There is no conflict of interest to declare. EDAT- 2013/06/07 06:00 MHDA- 2014/07/30 06:00 PMCR- 2015/01/01 CRDT- 2013/06/07 06:00 PHST- 2013/05/13 00:00 [accepted] PHST- 2013/06/07 06:00 [entrez] PHST- 2013/06/07 06:00 [pubmed] PHST- 2014/07/30 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.1002/j.1532-2149.2013.00343.x [doi] PST - ppublish SO - Eur J Pain. 2014 Jan;18(1):29-38. doi: 10.1002/j.1532-2149.2013.00343.x. Epub 2013 Jun 6.