Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model.

Abstract

Bone tumor pain is a poorly controlled pain comprising background and severe pain on moving or weight-bearing postures that decreases the quality of life for cancer patients; thus, more effective analgesics are clearly needed. This study evaluated the efficacy of a cannabinoid (CB) receptor agonist (WIN 55,212-2) on bone tumor pain in the spinal cords of rats, and clarified the roles of the CB1 and CB2 receptors in WIN 55,212-2-induced antinociception at the spinal level. Bone tumor pain was induced by injecting MRMT-1 tumor cells (1×10(5)) into the right tibias of female Sprague-Dawley rats under sevoflurane anesthesia. Bone tumor development was monitored radiologically. Under sevoflurane anesthesia, a polyethylene catheter was inserted into the intrathecal space for drug administration. To assess pain, the withdrawal threshold was measured by applying a von Frey filament to the tumor cell inoculation site. The effect of intrathecal WIN 55,212-2 was investigated. Next, the WIN 55,212-2-mediated antinociception was reversed using CB1 (AM 251) and CB2 (AM 630) receptor antagonists. The intratibial injection of MRMT-1 tumor cells produced radiologically confirmed bone tumors. The paw withdrawal threshold decreased significantly (mechanical allodynia) with tumor development; however, intrathecal WIN 55,212-2 dose-dependently increased the withdrawal threshold. The antinociceptive effect of WIN 55,212-2 was reversed by both CB1 and CB2 receptor antagonists. Intrathecal WIN 55,212-2 reduced bone tumor-related pain behavior mediated via spinal CB1 and CB2 receptors. Therefore, spinal CB receptor agonists may be novel analgesics in the treatment of bone tumor pain.

• Authors: Jin Hua Cui, Woong Mo Kim, Hyung Gon Lee, Ye Ok Kim, Chang Mo Kim, Myung Ha Yoon
• Journal: Neuroscience letters (Neurosci Lett) Vol. 493 Issue 3 Pg. 67-71 (Apr 15 2011) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 21195743 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Analgesics
• Benzoxazines
• Cannabinoids
• Morpholines
• Naphthalenes
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone

Topics

• Analgesics (administration & dosage)
• Animals
• Benzoxazines (administration & dosage)
• Bone Neoplasms (complications, drug therapy, physiopathology)
• Cannabinoids (administration & dosage, metabolism)
• Disease Models, Animal
• Female
• Injections, Spinal
• Morpholines (administration & dosage)
• Naphthalenes (administration & dosage)
• Pain (drug therapy, etiology, physiopathology)
• Pain Measurement (drug effects, methods)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (agonists, physiology)
• Receptor, Cannabinoid, CB2 (agonists, physiology)
• Spinal Neoplasms (complications, drug therapy, physiopathology)
• Tumor Cells, Cultured