Anti-nociceptive and anti-edematogenic effects of glibenclamide in a model of acute gouty attack in rats

We investigated the effect of glibenclamide on inflammatory parameters in a model of acute gouty attack in rats. Intra-articular injection of 50 mu l of monosodium urate (MSU) crystals (1.25 mg/site) was used to induce gout-related inflammation. The effects of glibenclamide (1-10 mg/kg, s.c.) or dexamethasone (8 mg/kg, s.c., positive control) were assessed on several inflammation parameters. Spontaneous nociception assessment, edema measurement, total and differential leucocyte counts, interleukin (IL)-1 beta release, prostaglandin E-2 production and determination of blood glucose levels were analyzed. Peritoneal macrophages were incubated with MSU and levels of IL-1 beta were measured. Statistical significance was assessed by one- or two-way analysis of variance. Glibenclamide (3 mg/kg) or dexamethasone (8 mg/kg) prevented nociception and edema induced by MSU injection in rats. Glibenclamide did not affect leukocyte infiltration, IL-1 beta release and PGE(2) production, but only reduced IL-1 beta production by MSU-stimulated macrophages at very high concentration (200 mu M). Dexamethasone significantly reduced leukocyte infiltration, IL-1 beta release and PGE(2) production. Glibenclamide reduced whereas dexamethasone increased blood glucose levels of MSU-injected rats. Glibenclamide reduced nociception and edema, but not leukocyte infiltration, IL-1 beta release and PGE(2) production. However, its substantial effect on nociception and edema suggests that glibenclamide can be an interesting option as an adjuvant treatment for pain induced by acute attacks of gout.