Effects of adrenal medullary transplants on pain-related behaviors following excitotoxic spinal cord injury

Abstract

Previous studies have shown that intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Significant changes in the functional properties of sensory neurons adjacent to the site of injury have also been observed in this model. Additionally, following QUIS injections, mechanical and cold allodynia, combined with excessive grooming behavior have been shown to be the behavioral correlates of these pathological and physiological changes. These behaviors are believed to be related to the clinical conditions of spontaneous and evoked pain following SCI. Given the therapeutic properties of adrenal chromaffin cell transplantation in conditions of neuropathic and cancer pain, it is proposed that the neuroactive substances released from chromaffin cells can alter or prevent the onset and progression of QUIS-induced behavioral changes. The effects of adrenal transplants were evaluated in 14 male Long-Evans rats that received intraspinal injections of QUIS. Pain behaviors, including the progression of excessive grooming behavior (n=8) and hypersensitivity to mechanical and thermal stimuli (n=6) were evaluated following transplantation. A 53% increase in mechanical thresholds was observed following adrenal transplants along with a 70% reduction in the area of skin targeted for excessive grooming. These behaviors were not affected in 11 animals receiving transplants of skeletal muscle. The effects of adrenal transplants on cold allodynia consisted of a stabilization of response latencies in contrast to the continued decrease in latencies, i.e., increased sensitivity, following transplants of skeletal muscle. The results are consistent with previous studies showing the therapeutic efficacy of adrenal chromaffin cell transplants in neuropathic pain, and support the use of this treatment strategy for the alleviation of chronic pain following spinal cord injury.