Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats
Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats
复制标题
右美托咪定和乌司他丁对长春新碱引起的大鼠神经病理性疼痛的协同作用
DOI：
10.1016/j.jpain.2017.06.007
复制
发表时间：
2017-11-01
期刊：
影响因子：
4
通讯作者：
Ouyang, Handong
中科院分区：
文献类型：
--
作者：
Nie, Bilin;Zhang, Subo;Ouyang, Handong
抗微管蛋白化疗药物，如长春新碱 (VCR)，经常引起周围神经性疼痛。它通常是永久性的，严重损害癌症患者的生活质量，并可能导致临床治疗的障碍。目前，还没有确定的治疗方法，并且许多批准用于治疗其他神经性疼痛的药物显示出很少或没有镇痛效果。因此，为患有化疗药物引起的神经性疼痛的患者寻找新的治疗策略以改善患者的生活质量至关重要。这项研究表明，鞘内注射右美托咪定 (DEX) 或腹腔注射乌司他丁 (UTI) 通过上调白细胞介素 10 的表达并激活背根神经节 (DRG) 中的 α(2)-肾上腺素能受体，显着减少 VCR 诱导的 Sprague Dawley 大鼠的机械异常性疼痛。此外，当 DEX 和 UTI 结合使用时，会产生协同相互作用，从而对抗 VCR 引起的神经性疼痛。 DEX 和 UTI 之间的这种协同相互作用可能部分归因于共同的镇痛途径，其中白细胞介素 -10 的上调通过激活大鼠背根神经节中的 α(2)-肾上腺素能受体发挥重要作用。 DEX和UTI联合使用不影响大鼠的血压、心率、镇静、运动评分、空间学习或记忆功能。所有这些都表明，DEX和UTI的联合使用是缓解VCR引起的大鼠神经性疼痛的有效方法。 观点：本文记录了DEX和UTI这两种广泛使用的药物之间针对VCR引起的神经性疼痛的协同相互作用。该研究结果为临床治疗化疗引起的周围神经病理性疼痛提供了潜在的靶点和新的给药方法。 (C) 2017 年，美国疼痛协会
Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the alpha(2)-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating alpha(2)-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats.Perspective: This article documents the synergistic interaction between 2 widely used drugs, DEX and UTI, against VCR-induced neuropathic pain. The results provide a potential target and novel drug administrated method for the clinical treatment of chemotherapy-induced peripheral neuropathic pain. (C) 2017 by the American Pain Society