Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain
Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain
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DOI：
10.1016/j.pbb.2008.04.021
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Heegaard, Anne-Marie
中科院分区：
文献类型：
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作者：
Hald, Andreas;Ding, Ming;Heegaard, Anne-Marie
骨恶性肿瘤引起的疼痛是最难完全控制的癌症疼痛类型之一，并可能进一步降低患者的生活质量。由外周炎症反应或神经损伤引起的慢性疼痛条件的动物模型对大麻素激动剂治疗有反应。然而，大麻素激动剂在人类中的使用可能会受到中枢神经系统相关副作用和耐受性发展的阻碍。在本研究中，我们研究了重复低剂量给药合成大麻素激动剂WIN 55,212-2对小鼠骨癌疼痛和神经性疼痛的影响。此外，我们还调查了与中枢神经系统相关的副作用和耐受性的发展。我们发现，在骨癌疼痛模型中，连续18天服用0.5 mg/kg/天可降低疼痛相关行为和脊髓胶质原纤维酸性蛋白的表达，但在神经性疼痛模型中无此作用。此外，该治疗策略未发现诱导可测量的中枢神经系统相关副作用或耐受性。通过显微计算机断层扫描（mu CT）评估的癌细胞活力测定和骨体积分数表明，这些影响不是由于癌症进展的变化。骨癌和神经性疼痛模型之间WIN 55,212-2疗效的差异可能反映了不同的疼痛产生机制，可用于设计新的治疗药物。(c) 2008爱思唯尔公司版权所有。
Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (mu CT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs. (c) 2008 Elsevier Inc. All rights reserved.