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首页> 外文期刊>Molecular pain >Activation of the P2X 7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats
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Activation of the P2X 7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats

机译：中脑导水管周围灰质中P2X 7受体的激活参与曲马多在骨癌疼痛大鼠中的镇痛作用

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Cancer pain is a well-known serious complication in metastatic or terminal cancer patients. Current pain management remains unsatisfactory. The activation of spinal and supraspinal P2X7 receptors plays a crucial role in the induction and maintenance mechanisms of various kinds of acute or chronic pain. The midbrain periaqueductal gray is a vital supraspinal site of the endogenous descending pain-modulating system. Tramadol is a synthetic, centrally acting analgesic agent that exhibits considerable efficacy in clinically relieving pain. The purpose of this study was to determine whether the activation of P2X7 receptor in the ventrolateral region of the periaqueductal gray (vlPAG) participates in the analgesic mechanisms of tramadol on bone cancer pain in rats. The bone cancer pain rat model was established by intratibial cell inoculation of SHZ-88 mammary gland carcinoma cells. The analgesic effects of different doses of tramadol (10, 20, and 40 mg/kg) were assessed by measuring the mechanical withdrawal threshold and thermal withdrawal latency values in rats by using an electronic von Frey anesthesiometer and radiant heat stimulation, respectively. Alterations in the number of P2X7 receptor-positive cells and P2X7 protein levels in vlPAG were separately detected by using immunohistochemistry and Western blot assay. The effect of intra-vlPAG injection of A-740003 (100 nmol), a selective competitive P2X7 receptor antagonist, on the analgesic effect of tramadol was also observed. The expression of P2X7 receptor in the vlPAG on bone cancer pain rats was mildly elevated, and the tramadol (10, 20, and 40?mg/kg) dose dependently relieved pain-related behaviors in bone cancer pain rats and further upregulated the expression of P2X7 receptor in the vlPAG. The intra-vlPAG injection of A-740003 pretreatment partly but significantly antagonized the analgesic effect of tramadol on bone cancer pain rats. The injection of tramadol can dose dependently elicit analgesic effect on bone cancer pain rats by promoting the expression of the P2X7 receptor in vlPAG.
机译：癌症疼痛是转移性或晚期癌症患者的众所周知的严重并发症。当前的疼痛管理仍不能令人满意。脊髓和脊髓上P2X 7 受体的激活在各种急性或慢性疼痛的诱导和维持机制中起着至关重要的作用。中脑导水管周围灰色是内源性降压调节系统的重要脊柱上位。曲马多是一种合成的中枢镇痛药，在临床缓解疼痛方面显示出可观的功效。这项研究的目的是确定导水管周围灰色（vlPAG）腹侧区P2X 7 受体的激活是否参与曲马多对大鼠骨癌疼痛的镇痛作用。通过胫骨细胞内接种SHZ-88乳腺癌细胞建立了骨痛模型。通过分别使用电子冯·弗雷麻醉仪和辐射热刺激测量大鼠的机械戒断阈值和热戒断潜伏时间值，评估了不同剂量的曲马多（10、20和40 mg / kg）的镇痛效果。采用免疫组织化学和Western blot方法分别检测vlPAG中P2X 7 受体阳性细胞数量和P2X 7 蛋白水平的变化。还观察到vlPAG内注射选择性竞争性P2X 7 拮抗剂A-740003（100 nmol）对曲马多的镇痛作用。骨癌疼痛大鼠的vlPAG中P2X 7 受体的表达轻度升高，曲马多（10、20和40？mg / kg）剂量依赖性缓解骨癌疼痛相关行为使大鼠疼痛，并进一步上调vlPAG中P2X 7 受体的表达。 v-PAG内注射A-740003进行了部分预处理，但明显拮抗了曲马多对骨癌疼痛大鼠的镇痛作用。曲马多注射液通过促进vlPAG中P2X 7 受体的表达，可以剂量依赖性地引起骨痛大鼠镇痛作用。

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