title: (-)-α-Bisabolol reduces orofacial nociceptive behavior in rodents.
abstract: The purposes of this study were to evaluate the anti-nociceptive effect of oral and topical administration of (-)-α-bisabolol (BISA) in rodent models of formalin- or cinnamaldehyde-induced orofacial pain and to explore the inhibitory mechanisms involved. Orofacial pain was induced by injecting 1.5% formalin into the upper lip of mice (20 μL) or into the temporomandibular joint (TMJ) of rats (50 μL). In another experiment, orofacial pain was induced with cinnamaldehyde (13.2 μg/lip). Nociceptive behavior was proxied by time (s) spent rubbing the injected area and by the incidence of head flinching. BISA (100, 200, or 400 mg/kg p.o. or 50, 100, or 200 mg/mL topical) or vehicle was administered 60 min before pain induction. The two formulations (lotion and syrup) were compared with regard to efficacy. The effect of BISA remained after incorporation into the formulations, and nociceptive behavior decreased significantly in all tests. The high binding affinity observed for BISA and TRPA1 in the molecular docking study was supported by in vivo experiments in which HC-030031 (a TRPA1 receptor antagonist) attenuated pain in a manner qualitatively and quantitatively similar to that of BISA. Blockers of opioid receptors, NO synthesis, and K+ATP channels did not affect orofacial pain, nor inhibit the effect of BISA. In conclusion, BISA had a significant anti-nociceptive effect on orofacial pain. The effect may in part be due to TRPA1 antagonism. The fact that the effect of BISA remained after incorporation into oral and topical formulations suggests that the compound may be a useful adjuvant in the treatment of orofacial pain.
authors.affiliation: Center of Experimental Biology (Nubex), University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil. lua.melo@utoronto.ca.|Faculty of Dentistry - Oral Physiology, University of Toronto, Toronto, ON, Canada. lua.melo@utoronto.ca.
authors.forename: Luana Torres
authors.initials: LT
authors.lastname: Melo
authors.affiliation: Center of Experimental Biology (Nubex), University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil.
authors.forename: Mariana Araújo Braz
authors.initials: MA
authors.lastname: Duailibe
authors.affiliation: Center of Experimental Biology (Nubex), University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil.
authors.forename: Luciana Moura
authors.initials: LM
authors.lastname: Pessoa
authors.affiliation: Health Sciences Center, University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil.
authors.forename: Flávio Nogueira
authors.initials: FN
authors.lastname: da Costa
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil.
authors.forename: Antonio Eufrásio
authors.initials: AE
authors.lastname: Vieira-Neto
authors.affiliation: Health Sciences Center, University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Vasconcellos Abdon
authors.affiliation: Center of Experimental Biology (Nubex), University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil.
authors.forename: Adriana Rolim
authors.initials: AR
authors.lastname: Campos
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives; D000284:Administration, Oral; D000287:Administration, Topical; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005157:Facial Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D005557:Formaldehyde; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D000081222:Monocyclic Sesquiterpenes; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D011485:Protein Binding; D011487:Protein Conformation; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000700:Analgesics; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C480976:Trpa1 protein, rat; D005557:Formaldehyde; C004497:bisabolol; D000171:Acrolein; C012843:cinnamaldehyde
keywords: (−)-α-Bisabolol; Anti-nociceptive agents; Orofacial pain; TRPA1; Temporomandibular joint; Terpenes