Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.
Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3 μg, i.t.) dose-dependently prolonged the tail-flick latency, whereas there were no changes with the injection of either cannabinoid CB1 (AM 251, 1 μg, i.t.) or CB2 (AM 630, 4 μg, i.t.) receptor antagonists. AM 251 (1 μg, i.t.), but not AM 630 (4 μg, i.t.), significantly inhibited the prolongation of the tail-flick latency induced by WIN-55,212-2 (3 μg, i.t.). In streptozotocin-induced diabetic mice, the tail-flick latency was significantly shorter than that in normal mice. A low dose of WIN-55,212-2 (1 μg, i.t.) significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice. The effect of WIN-55,212-2 (1 μg, i.t.) in streptozotocin-induced diabetic mice was significantly inhibited by AM 630 (4 μg, i.t.), but not AM 251 (1 μg). The selective cannabinoid CB2 receptor agonist L-759,656 (19 and 38 μg, i.t.) also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice, and this recovery was inhibited by AM 630 (4 μg, i.t.). The protein levels of cannabinoid CB1 receptors, CB2receptors and diacylglycerol lipase α, the enzyme that synthesizes endocannabinoid 2-arachidonoylglycerol, in the spinal cord were examined using Western blotting. The protein levels of both cannabinoid CB1 and CB2 receptors were increased in streptozotocin-induced diabetic mice, whereas the protein level of diacylglycerol lipase α was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2receptor agonists might have an ability to recover diabetic neuropathic pain.
Copyright © 2013. Published by Elsevier Ltd.
2-AG, 2-arachidonoylglycerol, ANOVA, Cannabinoid, DGL-α, Diabetes, Diacylglycerol lipase α, Neuropathic pain, STZ, Spinal cord, Streptozotocin, analysis of variance, diacylglycerol lipase α, streptozotocin
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