Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin test

This study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe) 2 ) in the formalin test. Mice were pre‐treated with (PhSe) 2 by the oral route (0.1–100 mg kg −1 ), 30 min before formalin injection. To address some of the mechanisms by which (PhSe) 2 inhibits formalin‐induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe) 2 was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe) 2 (10 mg kg −1 , p.o.) was prevented by intrathecal injection of K + channel blockers such as apamin and charybdotoxin (small‐ and large‐conductance Ca 2+ ‐activated K + channel inhibitors, respectively) and tetraethylammonium (TEA, a non‐selective voltage‐dependent K + channel inhibitor), but not glib‐enclamide (an ATP‐sensitive K + channel inhibitor). The antinociceptive action caused by (PhSe) 2 (10 mg kg −1 , p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (N ω ‐nitro‐ l ‐arginine, L‐NOARG) and the soluble guanylate cyclase inhibitors 1 H ‐[1,2,4]oxadiazolo[4,3‐ a ]quinoxalin‐1‐one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca 2+ and K + channel pathways in the antinociceptive effect caused by (PhSe) 2 .