Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, UK.
J Clin Invest. 2010 Nov;120(11):3745-52. doi: 10.1172/JCI43158. Epub 2010 Nov 1.
Mendelian heritable pain disorders have provided insights into human pain mechanisms and suggested new analgesic drug targets. Interestingly, many of the heritable monogenic pain disorders have been mapped to mutations in genes encoding ion channels. Studies in transgenic mice have also implicated many ion channels in damage sensing and pain modulation. It seems likely that aberrant peripheral or central ion channel activity underlies or initiates many pathological pain conditions. Understanding the mechanistic basis of ion channel malfunction in terms of trafficking, localization, biophysics, and consequences for neurotransmission is a potential route to new pain therapies.
孟德尔遗传性疼痛障碍为人类疼痛机制提供了新的见解,并提示了新的镇痛药物靶点。有趣的是,许多遗传性单基因疼痛障碍已被定位到编码离子通道的基因突变。转基因小鼠的研究也表明许多离子通道参与伤害感受和疼痛调节。异常的外周或中枢离子通道活性似乎是许多病理性疼痛状况的基础或起始因素。从运输、定位、生物物理学以及对神经递质传递的影响等方面来理解离子通道功能障碍的机制基础,可能是开发新的疼痛治疗方法的一个途径。