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Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.
Neuroscience 2013; 250:446-54N

Abstract

The role of spinal cannabinoid systems in neuropathic pain of streptozotocin (STZ)-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3μg, 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 STZ-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 STZ-induced diabetic mice. The effect of WIN-55,212-2 (1 μg, i.t.) in STZ-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 STZ-induced diabetic mice, and this recovery was inhibited by AM 630 (4 μg, i.t.). The protein levels of cannabinoid CB1 receptors, CB2 receptors and diacylglycerol lipase α (DGL-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 STZ-induced diabetic mice, whereas the protein level of DGL-α was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.

Authors+Show Affiliations

Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23892011

Citation

Ikeda, H, et al. "Activation of Spinal Cannabinoid CB2 Receptors Inhibits Neuropathic Pain in Streptozotocin-induced Diabetic Mice." Neuroscience, vol. 250, 2013, pp. 446-54.
Ikeda H, Ikegami M, Kai M, et al. Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice. Neuroscience. 2013;250:446-54.
Ikeda, H., Ikegami, M., Kai, M., Ohsawa, M., & Kamei, J. (2013). Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice. Neuroscience, 250, pp. 446-54. doi:10.1016/j.neuroscience.2013.07.040.
Ikeda H, et al. Activation of Spinal Cannabinoid CB2 Receptors Inhibits Neuropathic Pain in Streptozotocin-induced Diabetic Mice. Neuroscience. 2013 Oct 10;250:446-54. PubMed PMID: 23892011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice. AU - Ikeda,H, AU - Ikegami,M, AU - Kai,M, AU - Ohsawa,M, AU - Kamei,J, Y1 - 2013/07/24/ PY - 2013/03/19/received PY - 2013/07/04/revised PY - 2013/07/16/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/4/5/medline KW - 2-AG KW - 2-arachidonoylglycerol KW - DGL-α KW - SDS KW - STZ KW - TBS KW - TBST KW - Tris-buffered saline KW - Tris-buffered saline containing 0.1% Tween-20 KW - cannabinoid KW - diabetes KW - diacylglycerol lipase α KW - i.t. KW - intrathecal KW - neuropathic pain KW - sodium dodecyl sulfate KW - spinal cord KW - streptozotocin SP - 446 EP - 54 JF - Neuroscience JO - Neuroscience VL - 250 N2 - The role of spinal cannabinoid systems in neuropathic pain of streptozotocin (STZ)-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3μg, 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 STZ-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 STZ-induced diabetic mice. The effect of WIN-55,212-2 (1 μg, i.t.) in STZ-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 STZ-induced diabetic mice, and this recovery was inhibited by AM 630 (4 μg, i.t.). The protein levels of cannabinoid CB1 receptors, CB2 receptors and diacylglycerol lipase α (DGL-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 STZ-induced diabetic mice, whereas the protein level of DGL-α was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/23892011/Activation_of_spinal_cannabinoid_CB2_receptors_inhibits_neuropathic_pain_in_streptozotocin_induced_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00622-2 DB - PRIME DP - Unbound Medicine ER -