Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute neuropathic pain.
Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute neuropathic pain.
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Janus激酶抑制剂AG490对奥沙利铂引起的急性神经病理性疼痛的镇痛作用
DOI：
10.4103/1673-5374.235305
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发表时间：
2018-08
影响因子：
6.1
通讯作者：
Wang YP
中科院分区：
文献类型：
--
作者：
Li SF;Ouyang BS;Zhao X;Wang YP
神经病理性疼痛经常发生在奥沙利铂化疗期间。AG490已被证明对炎性疼痛具有拮抗作用，但其对奥沙利铂诱导的神经病理性疼痛的作用尚不清楚。本研究旨在观察AG490对单次奥沙利铂所致的急性神经病理性疼痛的镇痛作用，并探讨其可能的机制。本研究采用6 mg/kg奥沙利铂腹腔注射的方法，建立了奥沙利铂急性神经病理性疼痛模型。模型注射后第2天，分别以1、5、10 mg/kg的剂量注射AG490。测定对机械刺激的缩足阈值和对冷刺激的缩尾潜伏期。Western印迹法检测脊髓磷酸化信号转导和转录激活子3(p-STAT3)的表达。免疫组织化学方法检测p-STAT3和IL-6的免疫反应性。结果表明，AG490能显著提高大鼠的缩足阈值和缩尾潜伏期。不同剂量的AG490作用差异无统计学意义。AG490 10 mg/kg可降低急性神经病理性疼痛大鼠脊髓中p-STAT3的表达，减少p-STAT3和IL-6的免疫反应。这些结果证实了AG490可以减轻奥沙利铂诱导的急性神经病理性疼痛，并与抑制JAK/STAT3信号通路有关。
Neuropathic pain often occurs during chemotherapy with oxaliplatin. AG490 has been shown to exert an antagonistic effect on inflammatory pain, but its effect on oxaliplatin-induced neuropathic pain remains poorly understood. This study sought to observe the analgesic effect of AG490 on acute neuropathic pain induced by a single oxaliplatin treatment and to address the possible mechanism. In this study, we established a model of oxaliplatin-induced acute neuropathic pain by intraperitoneal injection of 6 mg/kg oxaliplatin. On day 2 after injection, models were intraperitoneally injected with 1, 5, or 10 mg/kg AG490. Paw withdrawal threshold to mechanical stimuli and tail withdrawal latency to cold stimuli were determined. Western blot assay was performed to detect the expression of spinal phosphorylated signal transducer and activator of transcription 3 (p-STAT3). Immunohistochemistry was used to determine the immunoreactivity of p-STAT3 and interleukin-6. Results demonstrated that paw withdrawal threshold and tail withdrawal latency were significantly increased by the treatment of AG490 in rats. There was no significant difference in the effect among the different doses of AG490. AG490 10 mg/kg decreased the expression of p-STAT3, the immunoreactivity of p-STAT3 and interleukin-6 in spinal cord of acute neuropathic pain rats. These findings confirm that AG490 can attenuate oxaliplatin-induced acute neuropathic pain and is associated with the inhibition in the JAK/STAT3 signaling pathway.
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影响因子：
4.5
作者：
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通讯作者：
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影响因子：
8.8
作者：
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