Intraspinal Plasticity Contributing to Autonomic Dysreflexia Following SCI

According to the University of Alabama National Spinal Cord Injury Statistical Center, there are over 250,000 spinal cord injured (SCI) patients in the US, with approximately 11,000 new injuries occurring each year (March 2002). The majority of victims are males (82%) and a major cause of SCI is motor vehicle accidents (37%, March 2002). A recent survey assessing the quality of life measures in the SCI population has highlighted that restoring bladder/bowel function and eliminatina autonomic dysreflexia are the first and second highest priorities above walking 1. Autonomic dysreflexia is a potentially life-threatening complication of spinal cord injuries that occur above the sixth thoracic (T) spinal segment (T6). It is present after complete as well as incomplete 8CI 2 and with an incidence of 50-90% 3-6. Autonomic dysreflexia is commonly triggered by noxious stimuli below the injury site 2,4, particularly by the distension of the pelvic viscera (bowel and bladder). It is characterized by severe hypertension due to sudden, massive discharge of the disinhibited sympathetic preganglionic neurons below the injury site, which when accompanied by baroreflex-mediated bradycardia defines this autonomic syndrome. Importantly, autonomic dysreflexia develops in a time-dependent, incremental manner with large responses to noxious stimuli elicited in the first couple days post-SCI (~ 30 mmHg), which can be attributed mostly to the loss of supraspinal inhibition of sympathetic preganglionic neurons 7. In contrast, by day 7 post-injury, the responses are smaller (-14 mmHg), which correlates with the transient atrophy of the denervated sympathetic preganglionic neurons below the site of injury 8. However, by 2 weeks post-injury the hypertensive responses become greater than 30 mmHg. These observations suggest that post-traumatic intraspinal plasticity contributes to the development of autonomic dysreflexia 5. We and others 9-11 have shown that the establishment of autonomic dysreflexia correlates with profuse sprouting of calcitonin gene-related peptide (CGRP+) primary afferent fibers, particularly into the L6/S1 spinal segment. Indeed, increased nociceptive input (CGRP+ primary afferent fibers) to the spinal cord may play an important role in the development of autonomic dysreflexia after SCI 9. Moreover, electrical activity in spinal interneurons, sympathetic nerve activity, and changes in blood pressure in response to noxious and nonnoxious somatic and visceral stimuli were exaggerated in chronic SCI rats 12. Evidently, intraspinal plasticity and disinhibited sympathetic preganglionic neurons after injury are crucial components in dysreflexic-hypertension. However, what no-one has illustrated thus far is the dynamic relationship between these two substrates in the development of autonomic dysreflexia at the neuroanatomical and electrophysiological level, which is proposal seeks to elucidate.