Autonomic dysreflexia and primary afferent sprouting after clip-compression injury of the rat spinal cord

Spinal cord injury leads to many forms of autonomic dysfunction including a utonomic dysreflexia, a condition involving recurrent episodes of paroxysma l hypertension and associated bradycardia. This hypertension may reach inte nsities that are life-threatening. We investigated autonomic dysreflexia an d the sprouting of central processes of primary afferent neurons (a potenti al mechanism for autonomic dysreflexia) in a clinically-relevant calibrated clip-compression model of spinal cord injury in the rat. Autonomic dysrefl exia was induced by colon distension in the conscious rats 2 weeks after se vere (50-g) clip compression injury of the spinal cord at the 4th thoracic segment. The central arbor of small-diameter primary afferent fibers in lam inae III-VII of the spinal cord dorsal horn was also assessed at 2 weeks af ter cord injury by quantitative morphometry, using calcitonin gene-related peptide as a marker. In response to colon distension, arterial pressure inc reased by 41 +/- 3 mmHg from a resting value of 109 +/- 4 mmHg, and heart r ate decreased by 124 +/- 13 beats/min from a value of 515 +/- 16 beats/min (n = 7). Minimal locomotor function was recovered by these rats: by 2 weeks after injury they attained scores of only 3.1 +/- 1.3 on the Basso, Beatti e and Bresnahan scale. Histopathology of the clip-compression lesion site i n the cord consisted of extensive central necrosis extending several segmen ts rostral and caudal to the lesion. Quantitative measures of the small-dia meter afferent arbors revealed significant increases in area ranging from 2 0-27% in thoracolumbar segments caudal to the injury (n = 5) in comparison to sham-injured rats (n = 6). A second study was done to assess the impact of severity of injury on the relationship between the size of the primary a fferent arbors and autonomic dysreflexia. At 2 weeks after milder (20-g) cl ip injury at T4, rats exhibited responses to colon distension that were not those associated with autonomic dysreflexia (n = 5). Arterial pressure inc reased by only 16 +/- 3 mmHg and heart rate tended to increase (+19 +/- 12 beats/min). These rats attained a locomotor score of 7.1 +/- 0.4 by 2 weeks . The lesions at the injury site also contained necrosis and mild cavitatio n within the gray matter. No change in the small-diameter afferent arbor wa s detected at 2 weeks after the 20-g clip injury at T4 (n = 6 rats). These findings suggest that after severe but not mild clip compression injury of the spinal cord, sprouting of the afferent component of the spinal reflex a rc contributes to the development of autonomic dysreflexia. Neither dysrefl exia, nor changes in the afferent arbor size occurred after mild cord injur y. This clinically relevant clip compression cord injury model, studied mor e frequently for locomotor function, is excellent for investigating mechani sms for the development of autonomic dysreflexia and strategies for its pre vention.