Intrinsically photosensitive retinal ganglion cells are the primary but not exclusive circuit for light aversion
Intrinsically photosensitive retinal ganglion cells are the primary but not exclusive circuit for light aversion
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DOI：
10.1016/j.exer.2012.09.012
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发表时间：
2012-12-01
影响因子：
3.4
通讯作者：
Gorin, Michael B.
中科院分区：
文献类型：
--
作者：
Matynia, Anna;Parikh, Sachin;Gorin, Michael B.
当正常水平的光引起从不舒服到衰弱的疼痛时，就会出现光过敏症（畏光症）。目前治疗光敏性疼痛的唯一方法是避光。了解光过敏机制的第一步是开发可靠的光厌恶动物行为测试，并确定启动这种反应所需的光感受器。开发了一种可靠的明/暗盒行为测定法，可以独立于焦虑测量光厌恶，从而可以直接测试小鼠光异常性疼痛的一种内表型。缺乏固有光敏视网膜神经节细胞（ipRGC）的小鼠对强光的厌恶程度降低，表明这些细胞是厌恶光的主要回路。用外源性阿片受体激动剂治疗的小鼠表现出显着增强的光厌恶，这不依赖于 ipRGC，这表明光的替代途径正在发挥作用。吗啡可增强视网膜对光的电生理反应，但水平较低。这表明，对于观察到的剧烈的光厌恶，阿片类药物也会使光异常性疼痛的中枢大脑区域变得敏感。总而言之，我们的结果表明，光厌恶至少有两种可分离的机制，光通过这些机制引起特定的异常性疼痛行为：基于 ipRGC 的初级回路和吗啡敏化暴露的次级 ipRGC 独立回路。这些模型将有助于描绘适用于光异常疼痛的上游光感觉通路和下游回避通路。由爱思唯尔有限公司出版
Photoallodynia (photophobia) occurs when normal levels of light cause pain ranging from uncomfortable to debilitating. The only current treatment for photoallodynia is light avoidance. The first step to understanding the mechanisms of photoallodynia is to develop reliable animal behavioral tests of light aversion and identify the photoreceptors required to initiate this response. A reliable light/dark box behavioral assay was developed that measures light aversion independently from anxiety, allowing direct testing of one endophenotype of photoallodynia in mice. Mice lacking intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit reduced aversion to bright light, suggesting these cells are the primary circuit for light aversion. Mice treated with exogenous p opiate receptor agonists exhibited dramatically enhanced light aversion, which was not dependent on ipRGCs, suggesting an alternative pathway for light is engaged. Morphine enhances retinal electrophysiological responses to light but only at low levels. This suggests that for the dramatic light aversion observed, opiates also sensitize central brain regions of photoallodynia. Taken together, our results suggest that light aversion has at least two dissociable mechanisms by which light causes specific allodynia behaviors: a primary ipRGC-based circuit, and a secondary ipRGC-independent circuit that is unmasked by morphine sensitization. These models will be useful in delineating upstream light sensory pathways and downstream avoidance pathways that apply to photoallodynia. Published by Elsevier Ltd.