光遗传学在神经痛外周机制研究中的应用

Neurophathic pain is a major causal of disability and loss of life quality. There is still no safe and effective therapy for it, which could be due to the ambiguity in the understanding of its mechanism. Central sensitization in neuropathic pain is partially attributed to an increasing input from the periphery. It is suggested that peripheral activity help to trigger, maintain and then modulate the central sensitization in pain pathway but there is no commonly accepted conclusion on which subtype in the primary afferents is responsible to such a sensitization, mainly due to the limitation in traditional methods. As we are showing in this grant, application of optogenetics is shedding some light on resolving this mystery. We are going to selectively express channelrhodopsin/halorhodopsin in the primary afferents of rat and using light to induce constant activation /inhibition of the primary afferents. By analyzing the behavior change with and without light stimuli in naïve animal and a neuropathic pain model, we will be able to reach a better understanding of which fiber mediates the development and maintenance of central sensitization in neuropathic pain.

神经痛严重影响人们工作学习，而且一直缺乏有效安全的治疗手段。外周神经活动对中枢的痛觉敏化起到促进，维持和调节的作用。由于传统研究方法的限制，对主要是由Abeta还是C神经纤维介导中枢敏化，还没有明确的结论。光遗传学的应用可以部分地突破传统方法的限制，在动物清醒状态下，选择性的激动或抑制某类神经纤维，其结果具有良好的时间精度和可重复性。我们计划使用病毒载体在大鼠外周神经组织选择性表达光敏通道channelrhodopsin 和halorhodopsin。在光刺激的作用下，通过整体动物行为学实验，分析和判定何种神经纤维介导了外周神经活动增强引起的中枢敏化，以及在神经损伤情况下，阻断该种神经活动是否足以逆转这个过程。