title: The involvement of the TRPA1 receptor in a mouse model of sympathetically maintained neuropathic pain.
abstract: Sympathetic fibres maintain some forms of neuropathic pain, but the underlying mechanisms are poorly understood. Therefore, this study investigated the possible involvement of transient receptor potential ankyrin 1 (TRPA1) and the role of the sympathetic nervous system (involved in sympathetically maintained neuropathic pain) in a model of neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) in mice. Systemic injection of the selective TRPA1 antagonist HC-030031 reversed the mechanical and cold allodynia that was induced by sciatic nerve chronic constriction injury (CCI). Nerve injury also sensitised mice to nociception, which was induced by the intraplantar injection of a low dose of the TRPA1 agonist allyl isothiocyanate without changing TRPA1 immunoreactivity in the injected paw. Furthermore, chemical sympathectomy produced by guanethidine largely prevented CCI-induced mechanical and cold allodynia. CCI also induced a norepinephrine-triggered nociception that was inhibited by an α-adrenoceptor antagonist, norepinephrine transporter block and monoamine oxidase inhibition. Finally, the peripheral injection of HC-030031 also largely reduced CCI-induced norepinephrine nociception and mechanical or cold allodynia. Taken together, the present findings reveal a critical role of TRPA1 in mechanical and cold hypersensitivity and norepinephrine hypersensitivity following nerve injury. Finally, our results suggest that TRPA1 antagonism may be useful to treat patients who present sympathetically maintained neuropathic pain.
authors.affiliation: Graduate Program in Pharmacology, Department of Physiology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Francielle de Vargas
authors.initials: Fde V
authors.lastname: Pinheiro
authors.affiliation: Graduate Program in Pharmacology, Department of Physiology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Jardel Gomes
authors.initials: JG
authors.lastname: Villarinho
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Cássia Regina
authors.initials: CR
authors.lastname: Silva
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: Oliveira
authors.affiliation: Graduate Program in Pharmacology, Department of Physiology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Kelly de Vargas
authors.initials: Kde V
authors.lastname: Pinheiro
authors.affiliation: Department of Pharmaceutical Chemistry, University of Ferrara, Ferrara, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Petri
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Mateus Fortes
authors.initials: MF
authors.lastname: Rossato
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Gustavo Petri
authors.initials: GP
authors.lastname: Guerra
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Health Sciences, University of the Extreme South of Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Maribel
authors.initials: M
authors.lastname: Antonello Rubin
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
authors.affiliation: Graduate Program in Pharmacology, Department of Physiology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Santa Catarina,Florianópolis, SC, Brazil. Electronic address: ferreiraj99@gmail.com.
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: Graduate Program in Pharmacology, Department of Physiology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Eunice
authors.initials: E
authors.lastname: André
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D059225:Nociception / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
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; D000700:Analgesics; D011687:Purines; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse
keywords: Adrenoceptor; Chronic constriction injury; Cold allodynia; Mechanical allodynia; Norepinephrine; TRPA1 antagonist