PMID- 26393428 OWN - NLM STAT- MEDLINE DCOM- 20160815 LR - 20220311 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 310 DP - 2015 Dec 3 TI - The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats. PG - 206-15 LID - S0306-4522(15)00861-1 [pii] LID - 10.1016/j.neuroscience.2015.09.042 [doi] AB - Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and alpha,beta-methylene adenosine triphosphate (alphabetameATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain and mechanical hyperalgesia. Mechanistic studies elucidating transcriptional or post-translational regulation of TRPA1 expression under pathological pain conditions should provide important basic information to further advance the treatment of craniofacial muscle pain conditions. CI - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Asgar, J AU - Asgar J AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA. FAU - Zhang, Y AU - Zhang Y AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA. FAU - Saloman, J L AU - Saloman JL AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA. FAU - Wang, S AU - Wang S AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA. FAU - Chung, M-K AU - Chung MK AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA. FAU - Ro, J Y AU - Ro JY AD - University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA; Kyung Hee University, School of Dentistry, Department of Oral Medicine, 1 Hoegi Dong, Dongdaemun Gu, Seoul, Republic of Korea. Electronic address: jro@umaryland.edu. LA - eng GR - R01 DE016062/DE/NIDCR NIH HHS/United States GR - DE019448/DE/NIDCR NIH HHS/United States GR - DE023846/DE/NIDCR NIH HHS/United States GR - R01 DE023846/DE/NIDCR NIH HHS/United States GR - R01 DE019448/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150921 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Oximes) RN - 0 (TRPA1 Cation Channel) RN - 0 (TRPC Cation Channels) RN - 0 (Trpa1 protein, rat) RN - 6384-92-5 (N-Methylaspartate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9007-81-2 (Freund's Adjuvant) RN - NYX13NT29D (alpha,beta-methyleneadenosine 5'-triphosphate) SB - IM MH - Adenosine Triphosphate/analogs & derivatives/pharmacology MH - Animals MH - Disease Models, Animal MH - Excitatory Amino Acid Agonists/toxicity MH - Freund's Adjuvant/adverse effects MH - Hyperalgesia/chemically induced/pathology MH - Male MH - Myalgia/*etiology/*pathology MH - Myositis/*complications MH - N-Methylaspartate/toxicity MH - Oximes/toxicity MH - Pain Threshold/drug effects/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - TRPA1 Cation Channel MH - TRPC Cation Channels/antagonists & inhibitors/*metabolism MH - Trigeminal Ganglion/*metabolism MH - Up-Regulation/drug effects/ethics PMC - PMC4633371 MID - NIHMS725170 OTO - NOTNLM OT - AP18 OT - craniofacial OT - muscle afferents OT - myositis OT - trigeminal ganglia COIS- CONFLICT OF INTEREST There is no conflict of interest to declare. EDAT- 2015/09/24 06:00 MHDA- 2016/08/16 06:00 PMCR- 2016/12/03 CRDT- 2015/09/23 06:00 PHST- 2015/03/11 00:00 [received] PHST- 2015/09/08 00:00 [revised] PHST- 2015/09/15 00:00 [accepted] PHST- 2015/09/23 06:00 [entrez] PHST- 2015/09/24 06:00 [pubmed] PHST- 2016/08/16 06:00 [medline] PHST- 2016/12/03 00:00 [pmc-release] AID - S0306-4522(15)00861-1 [pii] AID - 10.1016/j.neuroscience.2015.09.042 [doi] PST - ppublish SO - Neuroscience. 2015 Dec 3;310:206-15. doi: 10.1016/j.neuroscience.2015.09.042. Epub 2015 Sep 21.