PERIPHERAL NERVE REGENERATION AND DORSAL HORN SOMATOTOPY

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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.