PERIPHERAL NERVE REGENERATION AND DORSAL HORN SOMATOTOPY

神经横断后感觉神经元的外周再生导致原代感觉神经元与脊髓背角细胞之间正常精确的体位和模态特异性连接错位。这种错位导致失去正常的触觉敏锐度。周围神经病变还会导致其他常见症状，从相对无害的痛觉过敏到慢性疼痛综合征，如异位性疼痛和causalgia，这些症状通常由轻微的触觉刺激激活。虽然有些疾病可能是永久性的，最明显的是疼痛综合征，但其他疾病，如两点辨别和定位，可以随着时间的推移而显着改善。最近的研究已经确定了脊髓背角在再神经支配后的特殊变化，这可能有助于触觉敏锐度的恢复和慢性疼痛综合征的发病。现在已经证明，在周围神经横断和再生后，初级感觉神经元和背角细胞之间的突触的功效可以显着改变。这些变化的范围从输入的丢失到新的功能连接的形成。这种突触的可塑性导致了单一简明背角细胞的重组，接受性刺激已被证明可以进行新的生长。这种新的生长可以导致在浅表背角形成新的突触，这个区域通常只接收对疼痛刺激有反应的纤维的输入。这些新的异位突触可能与疼痛综合征有关。本项目的两个主要目标是：(1)结合行为学、生理学和解剖学的方法，确定对触觉敏锐度恢复至关重要的背角体切断术的恢复方面；(2)结合解剖免疫组织化学和生理记录技术，确定能够支持这些异位投射的感觉神经元的特定子集，以及它们在损伤后可能发生的神经化学和生理变化。这些研究结果将为建立旨在增强触觉灵敏度恢复的临床策略提供信息，同时减少周围神经再生后慢性平原的发生。

The peripheral regeneration of sensory neurons following nerve transection results in the misalignment of normally precise somatotopic and modality specific connections between primary sensory neurons and cells in the spinal dorsal horn. This misalignment results in the loss of normal tactile acuity. Peripheral nerve lesions also result in other common symptoms ranging from relatively innocuous hyperalgesia to chronic pain syndromes such as allodynia and causalgia that are often activated by light tactile stimuli. Although some disorders can be permanent, most notably the pain syndromes, others like two-point discrimination and localization can show marked improvement with time. Recent investigations have identified specific change sin the spinal dorsal horn following re-innervation that may contribute to both the recovery of tactile acuity and the onset of chronic pain syndromes. It has now been shown that efficacy of synapses between primary sensory neurons and dorsal horn cells can be dramatically altered following peripheral nerve transection and regeneration. These changes range from the loss of inputs to the formation of new functional connections. This synaptic plasticity results in the reorganization of single concise dorsal horn cell receptive stimulation have been shown to undergo new growth. This new growth can result in the formation of new synapses in the superficial dorsal horn, a region that normally receives input from fibers responsive only to painful stimuli. These novel ectopic synapses could obviously contribute to the pain syndromes. The two main goals of this project are: (1) to combine behavioral, physiological and anatomical methodologies to ascertain those aspects of recovery of dorsal horn somatotopy that are critical to recovery of tactile acuity; (2) to combine anatomical immunohistochemical and physiological recording techniques to identify the specific subset of sensory neurons capable of supporting these ectopic projections and what neurochemical and physiological changes they may undergo following injury. The results of these studies will provide information that could be instrumental in the establishment of clinical strategies designed to enhance recovery of tactile acuity, while reducing the occurrence of chronic plain following peripheral nerve regeneration.