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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.

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  • Authors+Show Affiliations

    ,

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

    , , , ,

    Source

    Neuroscience letters 493:3 2011 Apr 15 pg 67-71

    MeSH

    Analgesics
    Animals
    Benzoxazines
    Bone Neoplasms
    Cannabinoids
    Disease Models, Animal
    Female
    Injections, Spinal
    Morpholines
    Naphthalenes
    Pain
    Pain Measurement
    Rats
    Rats, Sprague-Dawley
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Spinal Neoplasms
    Tumor 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), pp. 67-71. doi: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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(10)01622-8 DB - PRIME DP - Unbound Medicine ER -