Studies in this laboratory and elsewhere have shown that transplants of adrenal chromaffin cells into the spinal subarachnoid space can result in reduction in """"""""pain"""""""" behaviors in rat models of persistent pain. In a continuation of this work, experiments are proposed using rats with persistent pain due to experimentally-induced arthritis or sciatic nerve constriction. Two primary goals will be addressed; these are: 1) to assess the safety of adrenal medullary and chromaffin cell transplants in the spinal subarachnoid space; and 2) to clarify the mechanisms of reduction of pain behaviors consequent to adrenal medullary transplants, with particular attention to analysis of the effects on neuroplastic remodeling and long-term neuropathological consequences of chronic pain. The """"""""safety"""""""" issue will be addressed by analysis of three factors: 1) motor and other physiological functions; 2) cerebrospinal fluid and blood serum, and 3) neuropathology in spinal cord tissues. The effects of adrenal medullary transplants on functional plasticity in the central nervous system will be examined in the animal pain models with a combination of behavioral measurements and measurements of immediate early gene expression in spinal and supraspinal structures. Evaluation of the benefits of transplants on long-term pathological processes will be examined histologically by analysis of spinal tissues for the presence of hyperchromatic (""""""""dark"""""""") neurons and for changes in the numbers of neurons expressing the inhibitory neurotransmitter GABA.
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