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(−)-α-Bisabolol reduces orofacial nociceptive behavior in rodents

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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.

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Acknowledgements

The authors would like to thank CAPES (Coordination of Continuing Higher Education), CNPq (National Council for Scientific and Technological Development), Funcap (Ceará State Foundation of Support for Scientific and Technological Development), and the Edson Queiroz Foundation (University of Fortaleza) for the fellowship, financial support, and infrastructure.

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Authors and Affiliations

  1. Center of Experimental Biology (Nubex), University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil

    Luana Torres Melo, Mariana Araújo Braz Duailibe, Luciana Moura Pessoa & Adriana Rolim Campos

  2. Faculty of Dentistry - Oral Physiology, University of Toronto, Toronto, ON, Canada

    Luana Torres Melo

  3. Health Sciences Center, University of Fortaleza (Unifor), Fortaleza, Ceará, Brazil

    Flávio Nogueira da Costa & Ana Paula de Vasconcellos Abdon

  4. Department of Biochemistry and Molecular Biology, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil

    Antonio Eufrásio Vieira-Neto

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  1. Luana Torres Melo
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  2. Mariana Araújo Braz Duailibe
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  3. Luciana Moura Pessoa
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Correspondence to Luana Torres Melo.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study protocol was in accordance with the ethical guidelines of the National Council for the Control of Animal Experimentation (CONCEA, Brazil) and was approved and registered under no. 003/12 by the institutional animal ethics committee (CEUA/UNIFOR).

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Melo, L.T., Duailibe, M.A.B., Pessoa, L.M. et al. (−)-α-Bisabolol reduces orofacial nociceptive behavior in rodents. Naunyn-Schmiedeberg's Arch Pharmacol 390, 187–195 (2017). https://doi.org/10.1007/s00210-016-1319-2

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