Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Autor: Santos SAAR; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., Damasceno MBMV; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., Sessle BJ; Department of Physiology and Faculty of Dentistry, University of Toronto, Toronto, Canada., Vieira-Neto AE; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., de Oliveira Leite G; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., Magalhães FEA; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil.; Department of Nutrition and Health, State University of Ceará, Fortaleza, Brazil., Tavares KCS; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., Benevides SC; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil., Campos AR; Experimental Biology Center, University of Fortaleza, Fortaleza, Brazil. adrirolim@unifor.br.; Universidade de Fortaleza Núcleo de Biologia Experimental, Av. Washington Soares, 1321 Edson Queiroz, Fortaleza, Ceará, Brazil. adrirolim@unifor.br.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1007/s00210-024-03475-z
Abstrakt: Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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