CXCL12/CXCR4/MAPK信号传导通路在CB2受体激动剂调节癌痛吗啡耐受中的作用和机制研究

Cancer pain has affected the quality of patients life seriously, morphine is most commonly used in the treatment of cancer pain. But morphine tolerance and morphine dependence limit its clinical application. Currently, the target and mechanism of morphine tolerance are unclear, which have attracted our attention. As is reported, cannabinoid receptor can alleviate inflammation pain, neuropathic pain, cancer pain and postoperative pain, while the expression of cannabinoid receptor 2 (CB2), chemokines CXCL12 /CXCR4 and opioid receptors are related to morphine tolerance. We previously approved that CB2 can alleviate the pain induced by morphine tolerance and prolong the time of morphine tolerance. In this study, we’ll explore the effects of CB2 on morphine tolerance through animal ethology and molecular experiments. Whether it could regulate the expression of CXCL12 / CXCR4 in the spinal cord and spinal dorsal root ganglion and its downstream signaling pathway can provide a new idea of morphine tolerance treatment to cancer pain.

癌痛严重影响了患者的生活质量，目前吗啡是治疗癌痛最常用的药物。由于吗啡产生耐受和依赖限制了吗啡在临床中的应用。探寻癌痛吗啡耐受治疗靶点和机制尚不清楚。大麻素受体能够减轻炎症、神经病理性疼痛、癌痛及术后痛，同时大麻素受体2（CB2）与趋化因子CXCL12/CXCR4、阿片受体与吗啡耐受具有相关性，我们前期验证了，CB2能够减轻癌痛吗啡耐受，延长吗啡耐受产生的时间。在本实验中，利用动物行为学和分子生物学实验探讨CB2受体对癌痛吗啡耐受的影响是否通过调节脊髓和脊髓背根神经节CXCL12/CXCR4的表达及其下游信号传导通路，为癌痛吗啡耐受治疗提供新思路。

癌痛严重影响了患者的生活质量，目前吗啡是治疗癌痛最常用的药物。由于吗啡产生耐受 和依赖限制了吗啡在临床中的应用。探寻癌痛吗啡耐受治疗靶点和机制尚不清楚。大麻素受体 能够减轻炎症、神经病理性疼痛、癌痛及术后痛，同时大麻素受体2（CB2）与趋化因子CXCL12 /CXCR4、阿片受体与吗啡耐受具有相关性，我们前期验证了CB2能够减轻癌痛吗啡耐受，延长吗啡耐受产生的时间。在本实验中，利用动物行为学和分子生物学实验探讨CB2受体对癌痛吗啡耐受的影响是否通过调节脊髓和脊髓背根神经节CXCL12/CXCR4的表达及其下游信号传导通路，为癌痛吗啡耐受治疗提供新思路。