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Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model.
Neurosci Lett. 2011 Apr 15; 493(3):67-71.NL

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Cui JH
The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea.
Kim WM
No affiliation info available
Lee HG
No affiliation info available
Kim YO
No affiliation info available
Kim CM
No affiliation info available
Yoon MH
No affiliation info available

MeSH

AnalgesicsAnimalsBenzoxazinesBone NeoplasmsCannabinoidsDisease Models, AnimalFemaleInjections, SpinalMorpholinesNaphthalenesPainPain MeasurementRatsRats, Sprague-DawleyReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Spinal NeoplasmsTumor Cells, Cultured

Pub Type(s)

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

Language

eng

PubMed ID

21195743

Citation

Cui, Jin Hua, et al. "Antinociceptive Effect of Intrathecal Cannabinoid Receptor Agonist WIN 55,212-2 in a Rat Bone Tumor Pain Model." Neuroscience Letters, vol. 493, no. 3, 2011, pp. 67-71.
Cui JH, Kim WM, Lee HG, et al. Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model. Neurosci Lett. 2011;493(3):67-71.
Cui, J. H., Kim, W. M., Lee, H. G., Kim, Y. O., Kim, C. M., & Yoon, M. H. (2011). Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model. Neuroscience Letters, 493(3), 67-71. https://doi.org/10.1016/j.neulet.2010.12.052
Cui JH, et al. Antinociceptive Effect of Intrathecal Cannabinoid Receptor Agonist WIN 55,212-2 in a Rat Bone Tumor Pain Model. Neurosci Lett. 2011 Apr 15;493(3):67-71. PubMed PMID: 21195743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model. AU - Cui,Jin Hua, AU - Kim,Woong Mo, AU - Lee,Hyung Gon, AU - Kim,Ye Ok, AU - Kim,Chang Mo, AU - Yoon,Myung Ha, Y1 - 2010/12/31/ PY - 2010/07/09/received PY - 2010/11/18/revised PY - 2010/12/22/accepted PY - 2011/1/4/entrez PY - 2011/1/5/pubmed PY - 2011/9/2/medline SP - 67 EP - 71 JF - Neuroscience letters JO - Neurosci Lett VL - 493 IS - 3 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/21195743/abstract/Antinociceptive_effect_of_intrathecal_cannabinoid_receptor_agonist_WIN_55212_2_in_a_rat_bone_tumor_pain_model_ DB - PRIME DP - Unbound Medicine ER -