Effect of Fluvoxamine on Carrageenan-Induced Paw Edema in Rats Evaluation of the Action Sites

The present study was designed to explore the anti-inflammatory effect of fluvoxamine, as a selective serotonin reuptake inhibitor (SSRI) anti-depressant, on carrageenan-induced paw edema in more details. At first, fluvoxamine was administered intra-peritoneally (2.5, 12.5, 25 and 50 mg Kg(-1)) 30 min before the subplantar injection of carrageenan. Fluvoxamine was also injected intra-peritoneally at a dose of 50 mg Kg(-1) 30 or 90 min after carrageenan injection. Then, fluvoxamine was given intra-cerebroventricularly (25, 50 and 100 μg/rat) and intra-thecally (25, 50 and 100 μg/rat) 30 min before the carrageenan challenge. Finally, the effect of mifepristone (5 mg Kg(-1)), an antagonist of the glucocorticoid receptor, on the anti-edema effect of fluvoxamine (50 mg Kg(-1)) was investigated. Results showed that intra-peritoneal (IP) administration of fluvoxamine before or after carrageenan injection considerably inhibited paw edema response at 4 h post-carrageenan (p < 0.001), but intra-cerebroventricular (i.c.v.) and intra-thecal (i.t.) injection of fluvoxamine did not alter the degree of paw swelling. The inhibitory effect of fluvoxamine was reduced by the pretreatment of mifepristone (p < 0.01). Our results suggest that IP administration of fluvoxamine produces a noticeable anti-inflammatory effect in the carrageenan-induced paw edema in rats and at least, a part of this effect is mediated through glucocorticoid receptor. Moreover, it seems unlikely that central sites have an important role in this inhibitory effect of fluvoxamine.