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Neurosci Lett. 2011 Apr 15;493(3):67-71. doi: 10.1016/j.neulet.2010.12.052. Epub 2010 Dec 31.

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

Author information

1
The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea.

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.

PMID:
21195743
DOI:
10.1016/j.neulet.2010.12.052
[Indexed for MEDLINE]

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