PT630. Influence of HMGB1 signaling in the global cerebral ischemia-induced mechanical allodynia

s | 31 1 Eskisehir Osmangazi University Medical School, Department of Pharmacology 2 Eskisehir Osmangazi University Medical School, Department of Anaesthesiology and Reanimation Abstract Objective: Curcumin, an active substance of the plant Curcuma longa, was reported to exhibit antiinflammatory, antioxidant, anticancer, antimicrobial ve antilipidemic features. The aim of this study is to investigate the antinociceptive effect of acute curcumin administration and the role of nitrergic, opioidergic, serotonergic and glutamaterjik pathways in mice. Methods: Male Swiss-albino mice (25–35 g) were randomly divided into 9 groups: control (dimethyl sulfoxide), tramadol 50 mg/kg (reference drug) curcumin 50, 100, 200mg/kg and combination of curcumin 200mg/kg with L-NAME 100mg/ kg, ketamine 10mg/kg, naloxone 1mg/kg and cyproheptadine 50μg/kg. Central antinociceptive activity was investigated with tail clip, tail flick and hot plate tests, and peripheral antinociceptive activity was determined with acetic acid-induced writhing test. Results: 100 and 200mg/kg curcumin increased the latency time compared to control in hot plate test which evaluates central supraspinal antinociception which was comparable to tramadol in curcumin 200mg/kg. This effect was enhanced in the combination of curcumin with L-NAME. Curcumin alone did not increase the latency time in tail flick and tail clip tests that evaluate central spinal antinociception while a significant increase in the latency time was observed in the combination of curcumin with cyproheptadine. Curcumin 100 and 200mg/ kg dose-dependently decreased the number of writhings compared to control in acetic acid induced writhing test more effective than tramadol. This peripheral antinociceptive effect was enhanced with the combination of cyproheptadine. Tramadol, significantly prolonged latency time compared to control group in hot plate test and decreased the number of writhings in acetic acid induced writhing test. Conclusion: We suggest that curcumin showed central supraspinal and peripheral antinociceptive effects especially in 200mg/ kg dose while it exerted a dose-dependent peripheral antinociceptive activity. Nitrergic and serotonergic pathways in the central and serotonergic pathway in the peripheral effects may be in involved in the antinociception elicited with curcumin.