Paclitaxel-induced peripheral neuropathy increases substance P release in rat spinal cord
Paclitaxel-induced peripheral neuropathy increases substance P release in rat spinal cord
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DOI：
10.1016/j.ejphar.2015.11.055
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发表时间：
2016-01-05
影响因子：
5
通讯作者：
Taguchi, Kyoji
中科院分区：
文献类型：
--
作者：
Chiba, Terumasa;Oka, Yusuke;Taguchi, Kyoji
周围神经病变是紫杉醇治疗的常见不良反应。紫杉醇的主要剂量限制性副作用是外周感觉神经病变，其特征在于手和脚的疼痛性感觉异常。为了分析P物质对紫杉醇诱导的机械性痛觉过敏的发展的贡献，分析了紫杉醇治疗后大鼠脊髓背角浅层中P物质的表达。使用von Frey试验和爪热试验进行的行为评估表明，腹膜内给予2和4 mg/kg紫杉醇在给药后7天和14天诱导机械异常性疼痛/痛觉过敏和热痛觉过敏。免疫组织化学显示，紫杉醇（4 mg/kg）治疗显著增加了脊髓背角浅层的P物质表达（第7天为37.6 +/- 3.7%，第14天为43.6 +/- 4.6%），而降钙素基因相关肽（CGRP）表达无变化。此外，紫杉醇（2和4毫克/公斤）治疗显着增加了P物质的释放在第14天的脊髓。这些结果表明，紫杉醇治疗增加了P物质的释放，但不是CGRP在脊髓背角的浅层，并可能有助于紫杉醇引起的疼痛性周围神经病变。(C)2015爱思唯尔B. V.保留所有权利。
Peripheral neuropathy is a common adverse effect of paclitaxel treatment. The major dose-limiting side effect of paclitaxel is peripheral sensory neuropathy, which is characterized by painful paresthesia of the hands and feet. To analyze the contribution of substance P to the development of paclitaxel-induced mechanical hyperalgesia, substance P expression in the superficial layers of the rat spinal dorsal horn was analyzed after paclitaxel treatment. Behavioral assessment using the von Frey test and the paw thermal test showed that intraperitoneal administration of 2 and 4 mg/kg paclitaxel induced mechanical allodynia/hyperalgesia and thermal hyperalgesia 7 and 14 days after treatment. Immunohistochemistry showed that paclitaxel (4 mg/kg) treatment significantly increased substance P expression (37.6 +/- 3.7% on day 7, 43.6 +/- 4.6% on day 14) in the superficial layers of the spinal dorsal horn, whereas calcitonin gene-related peptide (CGRP) expression was unchanged. Moreover, paclitaxel (2 and 4 mg/kg) treatment significantly increased substance P release in the spinal cord on day 14. These results suggest that paclitaxel treatment increases release of substance P, but not CGRP in the superficial layers of the spinal dorsal horn and may contribute to paclitaxel-induced painful peripheral neuropathy. (C) 2015 Elsevier B.V. All rights reserved.