中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (6): 1091-1098.doi: 10.4103/1673-5374.250631

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

参与慢性压迫性损伤致神经性疼痛中持续性痛觉过敏的发生机制

  

  • 出版日期:2019-06-15 发布日期:2019-06-15
  • 基金资助:

    中国国家自然科学基金项目（30160026），石河子大学高水平人才科研项目（RCSX201705）

Mechanism of persistent hyperalgesia in neuropathic pain caused by chronic constriction injury

Qin-Yi Chen 1, 2, 3 , Chao-Yang Tan 2, 3 , Yang Wang 2, 3 , Ke-Tao Ma 2, 3 , Li Li 2, 3 , Jun-Qiang Si 2, 3, 4   

  1. 1 Department of Anesthesiology, First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China
    2 Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China
    3 Key Laboratory of Xinjiang Endemic and Ethnic Disease, Shihezi University School of Medicine, Shihezi, Xinjiang Uygur Autonomous Region, China
    4 Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Jun-Qiang Si, PhD, sijunqiang@shzu.edu.cn; Li Li, PhD, lily7588@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 30160026 (to JQS); the High Level Talent Research Project of Shihezi University of China, No. RCSX201705 (to YW).

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摘要：

TMEM16A跨膜蛋白是一类涉及上皮分泌、感觉传导、伤害感受、神经元兴奋性控制和平滑肌收缩调节等多种生理功能的跨膜蛋白，可能是导致周围疼痛传导的重要分子之一。为了探索TMEM16A跨膜蛋白在慢性压迫性损伤致神经性疼痛中持续性痛觉过敏中的作用。实验以结扎左侧坐骨神经建立慢性压迫性损伤致神经性疼痛大鼠模型，然后在L5-6出植入鞘内导管通过导管注射10 μg TMEM16A跨膜蛋白抑制剂T16Ainh-A01。测量热痛时，于14d给药1次，以镇痛计记录热刺激后的退缩潜伏期；测量其余指标时，于12d时给药，每6h给药1次，共给药5次，于14d时进行检测，以Western blot分析L4-6背根神经节中TMEM16A的表达水平，以免疫荧光染色检测损伤侧L4-6背根神经节中TMEM16A跨膜蛋白的免疫阳性表达，以膜片钳技术检测L4-6背根神经节细胞中的电生理变化。结果显示，慢性压迫性损伤致神经性疼痛大鼠热刺激的退缩潜伏期缩短，L4-6背根神经节中TMEM16A跨膜蛋白的表达以及阳性细胞数量增加，诱发L4-6背根神经节细胞兴奋，而T16Ainh-A01可抑制上述表现。表明TMEM16A跨膜蛋白可能在慢性压迫性损伤致神经性疼痛中的痛觉过敏起关键作用，抑制TMEM16A跨膜蛋白可能为治疗神经性疼痛提供新的方法。

orcid: 0000-0001-6704-2115 (Jun-Qiang Si)
           0000-0001-8591-0676 (Li Li)

关键词: TMEM16A, 钙激活氯离子通道, T16Ainh-A01, 神经性疼痛, 背根神经节, 痛觉过敏, 动作电位, 基强度, 慢性压迫性损伤, 周围神经损伤, 神经再生

Abstract:

Transmembrane member 16A (TMEM16A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16A in the persistent hyperalgesia that results from chronic constriction injury-induced neuro¬pathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16A selective antagonist (10 μg T16Ain h-A01) was intrathecally injected at L5–6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and ther¬mal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days, once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TME¬M16A expression in the L4–6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16A in the L4–6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4–6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with con¬trol rats. Additionally, TMEM16A expression and the number of TMEM16A positive cells in the L4–6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4–6 dorsal root ganglion. These findings were inhibited by T16Ainh-A01 and confirm that TMEM16A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16A might be a novel pharmacological intervention for neuropathic pain.

Key words: nerve regeneration, TMEM16A, calcium-activated chloride channels, T16Ainh-A01, neuropathic pain, dorsal root ganglia, hyperalgesia, action potential, rheobase, chronic constriction injury, peripheral nerve injury, neural regeneration