Reduction of Bone Cancer Pain by Activation of Spinal Cannabinoid Receptor 1 and Its Expression in the Superficial Dorsal Horn of the Spinal Cord in a Murine Model of Bone Cancer Pain
Reduction of Bone Cancer Pain by Activation of Spinal Cannabinoid Receptor 1 and Its Expression in the Superficial Dorsal Horn of the Spinal Cord in a Murine Model of Bone Cancer Pain
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DOI：
10.1097/aln.0b013e3181a51e0d
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发表时间：
2009-07-01
期刊：
影响因子：
8.8
通讯作者：
Namiki, Akiyoshi
中科院分区：
文献类型：
--
作者：
Furuse, Shingo;Kawamata, Tomoyuki;Namiki, Akiyoshi
背景：骨癌疼痛对患者的生活质量影响较大，但治疗难度大。因此，需要开发一种新的治疗骨癌疼痛的策略来提高患者的生活质量。本研究探讨选择性脊髓大麻素受体1(CB1)的激活是否能减轻骨癌疼痛，并检测CBI在脊髓中的表达。方法：将肉瘤细胞植入小鼠股骨髓内造成骨癌疼痛模型。在行为学实验中，作者检测了脊髓CB1的激活和内源性大麻素代谢的抑制对骨癌相关疼痛行为的影响。结果：外源性给予CB1激动剂花生四烯基-2-氯乙酰胺激活脊髓CBI可减少骨癌相关疼痛行为，包括自发性疼痛行为和运动诱发疼痛行为。在免疫组织化学实验中，虽然Mu-阿片受体1在肉瘤细胞种植部位同侧浅背角的表达减少，但CB1的表达仍保持不变。此外，CBI主要在轴突终末表达，而在背角浅层的树突中不表达。结论：脊髓CBI的激活降低了骨癌相关的疼痛行为。突触前抑制可能参与了脊髓CBI激活的镇痛作用。这些发现可能会为骨癌疼痛的治疗带来新的策略。
Background: Bone cancer pain has a strong impact on the quality of life of patients, but it is difficult to treat. Therefore, development of a novel strategy for the treatment of bone cancer pain is needed for improvement of patient quality of life. This study examined whether selective spinal cannabinoid receptor 1 (CB1) activation alleviates bone cancer pain and also examined the spinal expression of CBI.Methods: A bone cancer pain model was made by implantation of sarcoma cells into the intramedullary space of the mouse femur. In behavioral experiments, the authors examined the effects of activation of spinal CB1 and inhibition of metabolism of endocannabinoid on bone cancer-related pain behaviors. Immunohistochemical experiments examined the distribution and localization of CB1 in the superficial dorsal horn of the spinal cord using specific antibodies.Results: Spinal CBI activation by exogenous administration of a CB1 agonist arachidonyl-2-chloroethylamide reduced bone cancer-related pain behaviors, including behaviors related to spontaneous pain and movement-evoked pain. in immunohistochemical experiments, although mu-opioid receptor 1 expression was reduced in the superficial dorsal horn ipsilateral to the site of implantation of sarcoma cells, CB1 expression was preserved. In addition, CBI was mainly expressed in the axon terminals, but not in the dendritic process in the superficial dorsal horn.Conclusion: Spinal CBI activation reduced bone cancer-related pain behavior. Presynaptic inhibition may contribute to the analgesic effects of spinal CBI activation. These findings may lead to novel strategies for the treatment of bone cancer pain.