Pereira, Elizete Maria RitaSouza, Jéssica MabelleCarobin, Natália VirtudeSilva, Juliana Figueira daAstoni, Duana Carvalho dos SantosSilva Júnior, Cláudio Antônio daBinda, Nancy ScarduaBorges, Marcia HelenaNagem, Ronaldo Alves PintoKushmerick, ChristopherFerreira, JulianoCastro Junior, Célio José deRibeiro, Fabiola MaraGomez, Marcus Vinicius2020-05-222020-05-222020PEREIRA, E. M. R. et al. Phoneutria toxin PnTx3-5 inhibits TRPV1 channel with antinociceptive action in an orofacial pain model. Neuropharmacology, v. 162, p. 107826, jan. 2020. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0028390819303922?via%3Dihub>. Acesso em: 10 fev. 2020.0028-3908http://www.repositorio.ufop.br/handle/123456789/12245Capsaicin, an agonist of TRPV1, evokes intracellular [Ca2+] transients and glutamate release from perfused trigeminal ganglion. The spider toxin PnTx3-5, native or recombinant is more potent than the selective TRPV1 blocker SB-366791 with IC50 of 47 ± 0.18 nM, 45 ± 1.18 nM and 390 ± 5.1 nM in the same experimental conditions. PnTx3-5 is thus more potent than the selective TRPV1 blocker SB-366791. PnTx3-5 (40 nM) and SB-366791 (3 μM) also inhibited the capsaicin-induced increase in intracellular Ca2+ in HEK293 cells transfected with TRPV1 by 75 ± 16% and 84 ± 3.2%, respectively. In HEK293 cells transfected with TRPA1, cinnamaldehyde (30 μM) generated an increase in intracellular Ca2+ that was blocked by the TRPA1 antagonist HC-030031 (10 μM, 89% inhibition), but not by PnTx3-5 (40 nM), indicating selectivity of the toxin for TRPV1. In whole-cell patch-clamp experiments on HEK293 cells transfected with TRPV1, capsaicin (10 μM) generated inward currents that were blocked by SB-366791 and by both native and recombinant PnTx3-5 by 47 ± 1.4%; 54 ± 7.8% and 56 ± 9.0%, respectively. Intradermal injection of capsaicin into the rat left vibrissa induced nociceptive behavior that was blocked by pre-injection with either SB-366791 (3 nmol/site i.d., 83.3 ± 7.2% inhibition) or PnTx3-5 (100 fmol/site, 89 ± 8.4% inhibition). We conclude that both native and recombinant PnTx3-5 are potent TRPV1 receptor antagonists with antinociceptive action on pain behavior evoked by capsaicin.en-USrestritoCapsaicinInhibitionArtigo publicado em periodicohttps://www.sciencedirect.com/science/article/pii/S0028390819303922?via%3Dihubhttps://doi.org/10.1016/j.neuropharm.2019.107826