Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain.
Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain.
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TRPM8在背根神经节中在神经损伤引起的慢性疼痛中的作用
DOI：
10.1186/1471-2202-12-120
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发表时间：
2011-11-23
期刊：
影响因子：
2.4
通讯作者：
Wang GL
中科院分区：
文献类型：
--
作者：
Su L;Wang C;Yu YH;Ren YY;Xie KL;Wang GL
慢性神经病理性疼痛是一种顽固性疼痛，几乎没有有效的治疗方法。温和的冷刺激可以缓解疼痛，这可能是探索新的镇痛方法的一种新思路。瞬时受体电位Melastatin 8(TRPM8)离子通道被认为是一种重要的冷分子传感器。采用坐骨神经慢性压迫损伤(CCI)大鼠模型，探讨TRPM8在慢性神经病理性疼痛发生机制中的作用。结果CCI大鼠术后第4天开始出现机械痛觉过敏、冷热痛觉过敏，术后第10~14天达高峰。损伤侧L5背根节(DRG)中TRPM8蛋白表达于伤后第4天显著升高，第10天达高峰，第14天仍维持在较高水平。TRPM8表达变化的时程与CCI诱导的后爪痛觉过敏反应的时程一致。鞘内注射薄荷脑激活CCI大鼠冷感受器TRPM8，可抑制机械性痛觉过敏和热痛觉过敏，增强冷痛觉过敏。相反，鞘内注射TRPM8反义寡核苷酸下调CCI大鼠同侧L5背根节TRPM8蛋白表达，可减轻冷痛敏反应，但对CCI诱导的机械性超敏和热痛敏无明显影响。结论TRPM8在神经损伤后形成的机械性超敏、冷痛敏和热痛敏中可能发挥不同的作用，为慢性神经末梢痛的新疗法的开发提供了一个很有前景的研究方向。
BackgroundChronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve.ResultsMechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia.ConclusionsTRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
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DOI：
10.1016/j.bbrc.2007.05.029
发表时间：
2007-07-13
影响因子：
3.1
作者：
Frederick, J.;Buck, M. E.;Cortright, D. N.
通讯作者：
Cortright, D. N.
影响因子：
5.3
作者：
Xing, Hong;Chen, Meng;Gu, Jianguo G.
通讯作者：
Gu, Jianguo G.
影响因子：
5.3
作者：
Premkumar, LS;Raisinghani, M;Pimentel, F
通讯作者：
Pimentel, F
影响因子：
5.7
作者：
Backonja, MM
通讯作者：
Backonja, MM
影响因子：
7.4
作者：
Knowlton WM;Bifolck-Fisher A;Bautista DM;McKemy DD
通讯作者：
McKemy DD