Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (6): 1091-1098.doi: 10.4103/1673-5374.250631

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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).

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