Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury

NEUROSCIENCE LETTERS

卷:566

Article

Xu, Qian^1,2  Cheong, Yong-Kwan^2,3  He, Shao-Qiu²  Tiwari, Vinod²  Liu, Jian⁴  Wang, Yun⁵  Raja, Srinivasa N.²  Li, Jinheng¹  Guan, Yun²  Li, Weiyan⁴ 

[1] Nanjing Univ, Jinling Hosp, Sch Med, Dept Clin Pharmacol, Nanjing 210008, Jiangsu, Peoples R China

[2] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA

[3] Wonkwang Univ, Sch Med, Dept Anesthesiol & Pain Med, Iksan, South Korea

[4] Nanjing Univ, Jinling Hosp, Sch Med, Dept Anesthesiol, Nanjing 210008, Jiangsu, Peoples R China

[5] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesiol, Beijing 100020, Peoples R China

关键词: Connexin 43;    Glia;    Gap junction;    Neuropathic pain;   

DOI  :  10.1016/j.neulet.2014.03.004

来源: Elsevier

【 摘 要 】

Activation of spinal astrocytes may contribute to neuropathic pain.Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3 mu g/15 mu l, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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