title: Role of hydrogen sulfide in the formalin-induced orofacial pain in rats.
abstract: Hydrogen sulfide (H2S) is a gasotransmitter synthesized in peripheral tissues by the enzyme cystathionine gamma-lyase (CSE). This gas has been documented to be involved in a wide variety of processes including inflammation and nociception. The aim of the present study was to investigate the role of the peripheral H2S pathway in nociceptive response to the orofacial formalin experimental model of pain. Orofacial pain was induced by subcutaneous injection of formalin (1.5%, 50 µl) into the upper lip of rats, and the time spent rubbing the face was measured at 3-min intervals for 45 min. Formalin induced a marked biphasic pain (first phase: 0-3 min; second phase: 15-33 min). Pretreatment with H2S donor (Na2S; 90 µmol/kg), CSE inhibitor (propargylglycine; 26.5 and 88.4 µmol/kg), or a preferential blocker of T-type Ca(2+) channels (mibefradil; 0.28 and 2.81 µmol/kg) attenuated the second phase of face rubbing when injected locally as well as systemically. Pretreatment with a selective blocker of K(+)ATP channels (glybenclamide; 2.81 µmol/kg) suppressed the Na2S-mediated attenuation of the formalin-induced pain second phase. Taken together these results suggest that endogenously produced H2S plays a pronociceptive role probably via T-type Ca(2+) channels, whereas exogenous H2S exerts antinociceptive effects mediated by K(+)ATP channels.
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Alberto F
authors.initials: AF
authors.lastname: Donatti
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rebeca M
authors.initials: RM
authors.lastname: Araujo
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renato N
authors.initials: RN
authors.lastname: Soriano
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Leopoldo U
authors.initials: LU
authors.lastname: Azevedo
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Christie A
authors.initials: CA
authors.lastname: Leite-Panissi
authors.affiliation: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil. Electronic address: branco@forp.usp.br.
authors.forename: Luiz G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000378:metabolism; D005157:Facial Pain / Q000139:chemically induced* / Q000378:metabolism* / Q000523:psychology; D005557:Formaldehyde / Q000009:adverse effects*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D054086:KATP Channels / Q000378:metabolism; D008046:Lip / Q000187:drug effects / Q000378:metabolism; D008297:Male; D059225:Nociception / Q000187:drug effects; D051381:Rats
chemical_list: D020747:Calcium Channels, T-Type; D054086:KATP Channels; D005557:Formaldehyde; D006862:Hydrogen Sulfide
keywords: Formalin test; H(2)S; K(+)(ATP) channels; T-type Ca(2+) channels