title: The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia.
abstract: Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel important in setting nociceptive threshold. It is expressed in nociceptive C-fibers and in non-neuronal cells involved in pro-inflammatory mediators' release. We asked whether TRPA1 contributes to carrageenan-induced hyperalgesia in rats, and if so, whether this contribution is mediated by mechanisms involved in inflammation such as cytokine release and neutrophil migration and/or by a direct sensitization of the primary afferent nociceptors. Pharmacological blockade of local TRPA1 by its selective antagonist HC 030031 prevented and reversed carrageenan-induced hyperalgesia, which was detected either by a mechanical or chemical (low dose of capsaicin) stimulus. However, it did not affect either carrageenan-induced cytokines expression or neutrophil migration. The neuronal TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodoexynucleotide completely prevented carrageenan-induced hyperalgesia over 24 h and significantly reduced TRPA1 expression in the dorsal root ganglia cells (L5-6), which was not affected by carrageenan treatment. We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan-induced inflammatory hyperalgesia by directly contributing to nociceptor excitability.
authors.affiliation: Department of Functional and Structural Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Ivan J M
authors.initials: IJ
authors.lastname: Bonet
authors.forename: Luana
authors.initials: L
authors.lastname: Fischer
authors.forename: Carlos Amílcar
authors.initials: CA
authors.lastname: Parada
authors.forename: Claudia H
authors.initials: CH
authors.lastname: Tambeli
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D002351:Carrageenan