title: Acute and neuropathic orofacial antinociceptive effect of eucalyptol.
abstract: Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-inflammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neuropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, capsaicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthenium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol. In a separate experiment, perinasal tissue levels of IL-1β, TNF-α and IFN-γ were measured. Rats were pretreated with eucalyptol before induction of temporomandibular joint pain with formalin or mustard oil. In another experiment, rats were submitted to infraorbital nerve transection (IONX) to induce chronic pain, followed by induction of mechanical hypersensitivity using Von Frey hairs. Locomotor performance was evaluated with the open-field test, and molecular docking was conducted on the TRPV1 channel. Pretreatment with eucalyptol significantly reduced formalin-induced nociceptive behaviors in all mouse strains, but response was more homogenous in the Swiss strain. Eucalyptol produced antinociceptive effects in all tests. The effect was sensitive to capsazepine but not to ruthenium red. Moreover, eucalyptol significantly reduced IFN-γ levels. Matching the results of the experiment in vivo, the docking study indicated an interaction between eucalyptol and TRPV1. No locomotor activity changes were observed. Our study shows that eucalyptol may be a clinically relevant aid in the treatment of orofacial pain, possibly by acting as a TRPV1 channel antagonist.
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.
authors.forename: José de Maria de Albuquerque de
authors.initials: JM
authors.lastname: Melo Júnior
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.
authors.forename: Marina de Barros Mamede Vidal
authors.initials: MB
authors.lastname: Damasceno
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.
authors.forename: Sacha Aubrey Alves Rodrigues
authors.initials: SA
authors.lastname: Santos
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.|Department of Physiology and Pharmacology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil.
authors.forename: Talita Matias
authors.initials: TM
authors.lastname: Barbosa
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.|Department of Biochemistry and Molecular Biology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil.
authors.forename: João Ronielly Campêlo
authors.initials: JR
authors.lastname: Araújo
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil.|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: Department of Physiology and Pharmacology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil.
authors.forename: Deysi Viviana Tenazoa
authors.initials: DV
authors.lastname: Wong
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil.
authors.forename: Roberto César Pereira
authors.initials: RC
authors.lastname: Lima-Júnior
authors.affiliation: Experimental Biology Center (NUBEX), University of Fortaleza (UNIFOR), Av. Washington Soares 1321, Edson Queiroz, Fortaleza, Ceará, CEP 60811-905, Brazil. adrirolim@unifor.br.
authors.forename: Adriana Rolim
authors.identifier: http://orcid.org/0000-0002-7355-9310
authors.initials: AR
authors.lastname: Campos
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000378:metabolism; D000077591:Eucalyptol; D005157:Facial Pain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation / Q000379:methods; D039821:Monoterpenes / Q000008:administration & dosage* / Q000378:metabolism; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D003511:Cyclohexanols; D039821:Monoterpenes; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000077591:Eucalyptol
keywords: Eucalyptol; IFN-γ; Orofacial nociception; TRPV1