Neuronal/Synaptic Reorganization after Partial Deafferentation

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Project concerns the plasticity of the neuronal and synaptic organization of the superficial dorsal horn of the spinal cord and of the somatosensory thalamus following partial deafferentation by constriction injury of peripheral nerve or specific lesions of spinothalamic tract neurons or their projects, respectively. We have already shown in the rat that sciatic nerve lesions that are models of human nerve injury result in profound alterations in the inhibitory circuitry of the dorsal horn in the first 3 to 21 days following nerve lesions, and that these changes in circuitry are directly correlated with pain behavior in the animals. We now wish to examine similar animals that survive for many months following nerve injury. Humans often have nerve injuries that result in major pain syndromes for many months and years, and we wish to determine whether rats with nerve injury eventually recover and whether we can identify the neural basis for the recovery. A parallel study of a model of diabetic neural basis for the recovery. A parallel study of a model of diabetic neuropathy, a common cause of pain and disability in humans, will be carried out with the laboratory of J. Levine, in which we will examine the saphenous nerve and the spinal cord in diabetic rats that exhibit hyperalgesia, as little is known about the possible changes that might occur in afferent pathways in diabetic neuropathy. In a collaborative study with HL Fields, we will determine whether specific lesions of spinothalamic tract neurons will result in the reorganization of the rat somatosensory thalamus. We will then extend these studies to examine possible deafferentation-induced changes in the organization of the thalamic nuclei in rat and monkey that project to the cingulate cortex, a region considered to be important in the emotional basis of emotional and aversive behavior in animals and humans with pain. We believe that our studies have a direct relevance to human pain syndromes and the results indicate that plastic changes in the neuronal circuitry of the somatosensory system may play a substantial role in the genesis and maintenance of pain. In people with injuries that result in partial deafferentation of major spinal cord and forebrain centers involved in the perception of, and the response to, pain, an understanding of nervous system changes is an important step in the design of therapies to treat human pain syndromes.