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On the Mechanisms Involved in Antinociception Caused by Local Administration of Diphenyl Diselenide
Lucielli Savegnago; Larissa Garcia Pinto; Cristiano Ricardo Jesse; Cristina Wayne Nogueira; Gilson Zeni
Departamento de Química – Laboratório de Síntese, Reatividade, Farmacologia e Toxicologia de Organocalcogênios – Universidade Federal de Santa Maria -Santa Maria – RS – Brasil.
The present study investigated some possible mechanisms involved in the local antinociceptive activity produced by diphenyl diselenide on glutamate-induced nociception and paw oedema. To address some mechanisms involved in local effect caused by diphenyl diselenide, distinct groups of animals were treated with different classes of drugs, all of them locally co-administered with glutamate (10 m mol/paw). In all experiments, after injection of drugs, mice were observed for 15 min and the amount of time spent licking the injected paw was recorded with a chronometer and was considered as indicative of nociception. At the end of each experiment, the paw oedema was also measured. To investigate the role played by the nitric oxide-L-arginine pathways in the antinociception caused by diphenyl diselenide, mice were pre-treated with L-arginine (60 m g/paw, i.pl., a nitric oxide precursor) and after 10 min received diphenyl diselenide (200 nmol/paw, i.pl.), NG-nitro-L-Arginine methyl ester (L-NAME,10 m g/paw, i.pl., an inhibitor of nitric oxide synthase-NOS) or vehicle (20 m L/paw), all drugs were administered in association with glutamate (10 m mol/paw), except L-arginine. To evaluate the involvement of redox modulatory site of glutamate receptors in nociceptive transmission a sulfhydryl reducing agent, dithiothreitol (DTT), and an oxidizing agent, 5,5’-dithio-bis-(2-nitrobenzoic acid) (DTNB), were tested. For this purpose, mice were pre-treated with DTT (0.3 m g/paw) and after 10 min they received diphenyl diselenide, DTNB (0.4 m g/paw, i.pl) or vehicle (20 m L/paw), all drugs were in association with glutamate (10 m mol/paw), except DTT. The local pre-treatment of mice with L-arginine, intraplantarly, restored antinociception caused by diphenyl diselenide. Pre-treatment of mice with DTT intraplantarly restored the local antinociception caused by diphenyl diselenide or DTNB. These results indicate that mechanisms of antinociception caused by diphenyl diselenide involve an interaction with not only nitrergic system but also via interaction with redox modulatory site of glutamate receptors.
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