Beneficial Effect of Cyclosporine in Experimental Diabetes Induced Neuropathic Pain in Rats

Abstract

The present study was designed to investigate the effect of cyclosporine on hyperglycemia induced decrease antinociceptive effect of morphine in rats. Streptozotocin (STZ) (50 mg kg-1, i.p., once) was administered to induce experimental diabetes in the rats. Pain sensitivity was measured using tail-flick and paw withdrawal test. Urinary and serum nitrite concentration was estimated using Greiss reagent. Spleen Homogenate Supernatant (SHS) was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 μL. i.v.) for 28 days. Experimental diabetes significantly decreased paw withdrawal latency to thermal stimuli on day 28 as compared to age matched control rats, indicating that diabetic rats exhibit thermal hyperalgesia. Moreover, analgesic effect of morphine (4 and 8 mg kg-1 s.c.), was progressively decreased in diabetic and SHS treated non diabetic rats. Further, the levels of nitric oxide were also elevated in 28th day diabetic and SHS treated non diabetic rats. However, administration of Cyclosporine (12.5 and 25 mg kg-1 i.p.), an IL-2 inhibitor and splenectomy attenuated diabetes and SHS induced decrease in nociceptive threshold and increase in serum and urinary nitrite levels. It is concluded that cyclosporine have beneficial effect in diabetic neuropathy and also improved the analgesic effect of morphine.