Zoology and International Collaboration on Repair Discoveries, 818 W. 10th Ave., Vancouver, BC, Canada.
Exp Neurol. 2012 May;235(1):70-7. doi: 10.1016/j.expneurol.2010.12.021. Epub 2010 Dec 30.
Neurons intrinsic to the spinal cord dorsal horn receive input from various classes of long-distance projection systems. Two of the best known of these are primary afferent and descending monoaminergic axons. Together with intrinsic interneurons, activity in these axonal populations shapes the early part of the sensory experience before it is transmitted to supraspinal structures via ascending projection axons. Injury to dorsal roots, which contain the centrally projecting branches of primary afferent axons, results in their permanent disconnection from the spinal cord, as well as sensory dysfunction such as pain. In animals, experimental dorsal root injuries affecting a small number of roots produce dynamic behavioural changes, providing evidence for the now familiar concept that sensory processing at the level of the spinal cord is not hard-wired. Changes in behaviour following rhizotomy suggest changes in spinal sensory circuitry, and we and others have shown that the density of spinal serotonergic axons as well as processes of inhibitory interneurons increases following rhizotomy. Intact primary afferent axons are less apt to sprout into denervated territory. Recent work from our group has asked (1) what is the stimulus that induces sprouting of serotonergic (and other) axons and (2) what prevents spared primary afferent axons from occupying the territory of those lost to injury. This article will review the evidence that a single factor upregulated by dorsal root injury, brain-derived neurotrophic factor (BDNF), underpins both serotonergic sprouting and a lack of primary afferent plasticity. BDNF also differentially modulates some of the behavioural consequences of dorsal root injury: antagonizing endogenous BDNF improves spontaneous mechanosensory recovery but prevents recovery from rhizotomy-induced hypersensitivity to cold. These findings reinforce the notion that in disease states as complex and variable as spinal cord injury, single pharmacological interventions are unlikely to produce meaningful results. However, understanding the differences in capacity for plasticity among different systems, as well as their triggers, should allow for more patient-tailored therapies.
脊髓背角固有神经元接收来自各种长程投射系统的输入。其中两个最为人所知的是初级传入和下行单胺能轴突。与固有中间神经元一起，这些轴突群体的活动在感觉体验的早期阶段塑造了感觉体验，然后通过上行投射轴突传递到脊髓上结构。背根损伤会导致其中包含初级传入轴突中枢投射分支的背根永久性断开，从而导致感觉功能障碍，如疼痛。在动物中，影响少数根的实验性背根损伤会产生动态行为变化，为现在熟悉的概念提供了证据，即脊髓水平的感觉处理不是固定不变的。根切断术后的行为变化表明脊髓感觉回路发生了变化，我们和其他人已经表明，脊神经节后 5-羟色胺能轴突的密度以及抑制性中间神经元的过程在根切断术后增加。完整的初级传入轴突不太容易向去神经支配的区域发芽。我们小组的最近研究提出了以下问题：（1）是什么刺激诱导 5-羟色胺能（和其他）轴突的发芽，（2）是什么阻止未受损的初级传入轴突占据因损伤而丧失的轴突的区域。本文将回顾证据表明，背根损伤上调的单个因子，脑源性神经营养因子（BDNF），为 5-羟色胺能的发芽和缺乏初级传入可塑性提供了基础。BDNF 还不同程度地调节了背根损伤的一些行为后果：拮抗内源性 BDNF 可改善自发性机械感觉恢复，但可防止因根切断术引起的对冷的超敏反应恢复。这些发现强化了这样一种观点，即在像脊髓损伤这样复杂多变的疾病状态下，单一的药物干预不太可能产生有意义的结果。然而，了解不同系统之间可塑性的差异及其触发因素，应该可以为更个体化的治疗方法提供依据。
