Lack of evidence for ectopic sprouting of genetically labeled Aβ touch afferents in inflammatory and neuropathic trigeminal pain.
Lack of evidence for ectopic sprouting of genetically labeled Aβ touch afferents in inflammatory and neuropathic trigeminal pain.
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DOI：
10.1186/s12990-015-0017-2
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发表时间：
2015-04-10
期刊：
影响因子：
3.3
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen Y;Liedtke W;Wang F
机械性特别是触觉痛觉超敏是慢性疼痛的一个标志，在这种情况下，无害的触摸会变得疼痛。先前基于霍乱毒素B（CTB）的神经追踪实验和电生理学研究表明，损伤后从触觉感觉传入纤维到疼痛处理层的异常轴突萌发可能是机械性痛觉超敏的解剖学基础。这一假设后来受到了使用A纤维神经元轴突内标记以及电生理鉴定的感觉神经元单神经元标记实验的挑战。然而，没有研究使用基因标记的神经元来研究这个问题，而且大多数研究是在脊髓感觉神经元上进行的，而不是三叉神经感觉神经元，而三叉神经感觉神经元是与口面部疼痛相关的神经元，在口面部疼痛中痛觉超敏常常起主要的临床作用。
我们最近发现，小白蛋白::Cre（Pv::Cre）标记三叉神经节中的两种Aβ触觉神经元。使用Pv::CreER驱动子和Cre依赖的报告小鼠，我们在炎症或眶下神经损伤（眶下神经横断）之前通过定时注射他莫昔芬特异性标记这些Aβ三叉触觉传入纤维。然后我们检查了损伤组与对照组相比标记轴突在脑干尾核的外周和中枢投射。我们没有发现Pv::CreER标记的三叉Aβ轴突异位萌发进入三叉神经浅感觉伤害性感受层的证据。此外，也没有外周萌发的证据。
损伤前基于CreER的标记排除了损伤后神经元表型变化的问题。我们的结果表明，慢性口面部疼痛中的触觉痛觉超敏不太可能是由Aβ三叉神经传入纤维的异位萌发引起的。
Mechanical and in particular tactile allodynia is a hallmark of chronic pain in which innocuous touch becomes painful. Previous cholera toxin B (CTB)-based neural tracing experiments and electrophysiology studies had suggested that aberrant axon sprouting from touch sensory afferents into pain-processing laminae after injury is a possible anatomical substrate underlying mechanical allodynia. This hypothesis was later challenged by experiments using intra-axonal labeling of A-fiber neurons, as well as single-neuron labeling of electrophysiologically identified sensory neurons. However, no studies have used genetically labeled neurons to examine this issue, and most studies were performed on spinal but not trigeminal sensory neurons which are the relevant neurons for orofacial pain, where allodynia oftentimes plays a dominant clinical role. We recently discovered that parvalbumin::Cre (Pv::Cre) labels two types of Aβ touch neurons in trigeminal ganglion. Using a Pv::CreER driver and a Cre-dependent reporter mouse, we specifically labeled these Aβ trigeminal touch afferents by timed taxomifen injection prior to inflammation or infraorbital nerve injury (ION transection). We then examined the peripheral and central projections of labeled axons into the brainstem caudalis nucleus after injuries vs controls. We found no evidence for ectopic sprouting of Pv::CreER labeled trigeminal Aβ axons into the superficial trigeminal noci-receptive laminae. Furthermore, there was also no evidence for peripheral sprouting. CreER-based labeling prior to injury precluded the issue of phenotypic changes of neurons after injury. Our results suggest that touch allodynia in chronic orofacial pain is unlikely caused by ectopic sprouting of Aβ trigeminal afferents.
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