Neurotropin alleviates rat osteocarcinoma pain via P(2)X(3) receptor activation in the midbrain periaqueductal gray.
Neurotropin alleviates rat osteocarcinoma pain via P(2)X(3) receptor activation in the midbrain periaqueductal gray.
复制标题
Neurotropin 通过中脑导水管周围灰质 P2X3 受体激活减轻大鼠骨癌疼痛
DOI：
10.22038/ijbms.2021.57965.12904
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发表时间：
2021-10
影响因子：
2.2
通讯作者：
Xiao Z
中科院分区：
文献类型：
--
作者：
Liu X;He J;Xiao Z
目的：对骨癌患者进行临床有效的镇痛治疗可减轻疼痛强度。中脑导水管周围灰质 (PAG) 在疼痛调节中发挥着关键作用，该区域 P2X3 受体的激活可介导疼痛处理。 Neurotropin 是一种小分子药物，用于多种慢性疼痛的镇痛治疗。本研究旨在确定 PAG 中 P2X3 受体的激活是否与 Neurotropin 对骨癌疼痛大鼠的镇痛作用有关。材料与方法：雌性Sprague-Dawley大鼠胫骨接种乳腺癌细胞，建立骨癌疼痛模型。腹腔注射 6、12 和 18 神经营养素单位 (NU)/kg 对腹外侧 PAG (vlPAG) 中疼痛阈值和 P2X3 受体表达的影响进行了评估。将 P2X3 受体拮抗剂 A-317491 (1.5 nmol/0.3 µl) 与高剂量神经营养素 (18 NU/kg) 一起注射到 vlPAG 中，以确定该受体在镇痛作用中的作用。结果：接种骨癌细胞后，骨癌痛大鼠的痛阈持续降低，而vlPAG中P2X3受体表达仅略有升高。 Neurotropin 以剂量依赖性方式显着提高 vlPAG 中的疼痛阈值和 P2X3 受体表达。将 A-317491 显微注射到 vlPAG 中，显着降低了 Neurotropin 对患有骨癌疼痛的大鼠的镇痛作用。结论：通过这些研究结果表明，vlPAG P2X3 受体激活参与了神经营养素介导的骨癌疼痛镇痛机制。
Objective(s): Clinically effective analgesia treatment for patients afflicted with osteocarcinoma lessens the intensity of pain. The midbrain periaqueductal gray (PAG) plays a critical role in pain modulation, and activation of P2X3 receptors in this region mediates pain processing. Neurotropin is a small molecule drug used for analgesic treatment of a number of chronic pain conditions. The present study aims at determining whether P2X3 receptor activation in PAG is responsible for the analgesic effect of neurotropin in rats with osteocarcinoma pain. Materials and Methods: The tibia of female Sprague-Dawley rats was inoculated with breast carcinoma cells to establish the osteocarcinoma pain model. The effects of intraperitoneal injection of 6, 12, and 18 neurotropin units (NU)/kg on pain threshold and receptor expression of P2X3 in the ventrolateral PAG (vlPAG) were assessed. The P2X3 receptor antagonist A-317491 (1.5 nmol/0.3 µl) was administered into vlPAG with a high-dose neurotropin (18 NU/kg) to determine the role of this receptor in the analgesic effect. Results: The pain thresholds of the rats with osteocarcinoma pain continuously decreased, whereas P2X3 receptor expression in vlPAG only slightly increased after osteocarcinoma cell inoculation. Neurotropin substantially elevated the pain threshold and P2X3 receptor expression in vlPAG in a dose-dependent manner. A-317491 microinjection into vlPAG significantly reduced the analgesic effects of neurotropin in the rats with osteocarcinoma pain. Conclusion: Through these findings, it is shown that vlPAG P2X3 receptor activation participates in neurotropin-mediated analgesia mechanism in osteocarcinoma pain.