title: The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.
abstract: 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 α,β-methylene adenosine triphosphate (αβmeATP), 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.
authors.affiliation: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: J
authors.initials: J
authors.lastname: Asgar
authors.affiliation: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Saloman
authors.affiliation: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, 650 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: M-K
authors.initials: MK
authors.lastname: Chung
authors.affiliation: 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.
authors.forename: J Y
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005620:Freund's Adjuvant / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology; D008297:Male; D063806:Myalgia / Q000209:etiology* / Q000473:pathology*; D009220:Myositis / Q000150:complications*; D016202:N-Methylaspartate / Q000633:toxicity; D010091:Oximes / Q000633:toxicity; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000941:ethics
chemical_list: C000602225:4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime; D018690:Excitatory Amino Acid Agonists; D010091:Oximes; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D016202:N-Methylaspartate; D000255:Adenosine Triphosphate; D005620:Freund's Adjuvant; C002630:alpha,beta-methyleneadenosine 5'-triphosphate
keywords: AP18; craniofacial; muscle afferents; myositis; trigeminal ganglia