Mechanisms involved in the antinociceptive and anti-inflammatory effects of bis selenide in mice

Objectives The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)-2,3 -bis(4-chlorophenylselanyl)prop-2-en-1-ol]. Methods The effects of oral his selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12-myristate 13-acetate (PMA), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) and prostaglandin E-2. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide. Key findings Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66-39.45) and 15.86 (12.17-20.67) mg/kg and maximal inhibition of 65 +/- 3% and 90 +/- 1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31 +/- 2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, his selenide caused a significant inhibition (42 +/- 5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64 3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE(2), PMA and 8-BrcAMP. The antinociceptive effect of his selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5-HT2A receptor antagonist), ondansetron (a 5-HT3 receptor antagonist) and ranitidine (a histamine H-2-receptor antagonist). Conclusions Glutamatergic, prostaglandin E-2, serotonergic (5-HT2A and 5-HT3) and histamine H-2 receptors are involved in the antinociceptive effects of his selenide in mice. The interaction of his selenide with protein kinase C and A signalling pathways was also demonstrated.