中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (8): 1471-1476.doi: 10.4103/1673-5374.235305

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

Janus激酶抑制剂AG490对奥沙利铂诱导的急性神经痛可发挥镇痛效应

  

  • 收稿日期:2018-01-29 出版日期:2018-08-15 发布日期:2018-08-15
  • 基金资助:

    中国国家自然科学基金项目（81671962）

Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute neuropathic pain

Shuang-Feng Li1, 2, Bi-Shan Ouyang2, Xin Zhao3, Ya-Ping Wang1   

  1. 1 Department of Anesthesiology, The Second Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
    2 Department of Anesthesiology, Hainan General Hospital, Haikou, Hainan Province, China
    3 Department of Neurology, Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
  • Received:2018-01-29 Online:2018-08-15 Published:2018-08-15
  • Contact: Ya-Ping Wang, Ph.D.,Wangyaping6568@csu.edu.cn
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81671962

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摘要：

 

在使用奥沙利铂进行化疗的过程中常会发生神经性疼痛这种严重的副作用。有研究发现AG490对于炎症性疼痛有对抗效应，但对奥沙利铂导致的神经性疼痛能否有作用尚不清楚。实验拟观察AG490对奥沙利铂诱导急性神经病理性疼痛的镇痛作用并探索其机制。首先以单次腹腔注射6mg/kg奥沙利铂建立急性神经性疼痛模型，然后在注射后第2天腹腔注射1，5，10mg/kg AG490进行干预。对大鼠进行冷和机械疼痛刺激评价疼痛阈值，以western blot检测脊髓中磷酸化STAT3的表达水平，以免疫组化检测脊髓中磷酸化STAT3和细胞介素6的免疫阳性反应。结果发现经AG490治疗后，急性神经性疼痛大鼠冷和机械刺激阈值明显增加，且不同剂量的AG490效果没有明显差异；10mg/kg AG490可使急性神经性疼痛大鼠脊髓中磷酸化STAT3表达以及磷酸化STAT3和细胞介素6的免疫阳性反应下降。表明AG490能够减弱奥沙利铂诱导的急性神经性疼痛，且这种作用可能与抑制JAK/STAT3信号传导通路有关。

orcid:0000-0001-6010-095X(Ya-Ping Wang)

关键词: 神经再生, AG490, 镇痛, 奥沙利铂, 癌症化疗, 神经性疼痛, 磷酸化STAT3, JAK/STAT信号通路, 白细胞介素6

Abstract:

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.

Key words: nerve regeneration, AG490, analgesia, oxaliplatin, cancer chemotherapy, neuropathic pain, phosphorylated STAT3, JAK/STAT signaling pathway, interleukin-6, neural regeneration