脊髓背角同步化放电在癌性爆发痛中的作用及其Cx43/GLT-1分子调控机制

癌性爆发痛是临床上的一类难治性癌痛，发作迅速、疼痛剧烈，严重影响病人生活质量。以往由于缺乏合适的动物模型，其发病机制并不清楚。我们前期用肿瘤内局部注射ET-1的方法成功建立了诱导型骨转移癌性爆发痛小鼠模型（PMID: 26828300），发现：模型小鼠癌性爆发痛发作时，L4、L5节段的脊髓背角发生了高度同步化的神经元放电，同时伴有星形胶质细胞中的Cx43表达上调和GLT-1表达下调。我们推测：脊髓背角神经元同步化放电是癌性爆发痛发作的电生理基础，该过程受Cx43和GLT-1调控。本课题拟通过离体和在体实验，采用电生理学、疼痛行为学和分子生物学等方法验证该假设。这些结果将为癌性爆发痛新机制的提出和临床干预提供理论依据。

Breakthrough cancer pain is a type of refractory cancer pain with rapid onset and severe pain clinically. It seriously affects the quality of life in patients. The exact pathogenesis and associated mechanism of breakthrough cancer pain are still not clear due to lack of suitable animal models. We successfully established a mouse model of inducible breakthrough cancer pain previously by local injection of ET-1 (PMID: 26828300). In the study, we observed that the neurons in spinal dorsal horn of the L4 and L5 segments had highly synchronized discharges with increased expression of Cx43 and decreased expression of GLT-1 in the astrocytes during the onset of pain in the mice. Therefore, we speculate that the synchronized bursting of neurons in the spinal dorsal horn is the electrophysiological basis for the onset of breakthrough cancer pain and this process may be regulated by Cx43 and GLT-1. This subject aims to use the methods of electrophysiology, pain behavior and molecular biology to validate the hypothesis in vitro and in vivo, and to provide the scientific basis for elucidating the new pathogenesis, molecular mechanism and effectively clinical intervention for breakthrough cancer pain.