Spinal cord injury leads to many forms of autonomic dysfunction including
autonomic dysreflexia, a condition involving recurrent episodes of paroxysmal
hypertension and associated
bradycardia. This
hypertension may reach intensities that are life-threatening. We investigated
autonomic dysreflexia and the sprouting of central processes of primary afferent neurons (a potential mechanism for
autonomic dysreflexia) in a clinically-relevant calibrated
clip-compression model of
spinal cord injury in the rat.
Autonomic dysreflexia was induced by colon distension in the conscious rats 2 weeks after severe (50-g)
clip compression injury of the spinal cord at the 4th thoracic segment. The central arbor of small-diameter primary afferent fibers in laminae III-VII of the spinal cord dorsal horn was also assessed at 2 weeks after cord injury by quantitative morphometry, using
calcitonin gene-related peptide as a marker. In response to colon distension, arterial pressure increased by 41 +/- 3 mmHg from a resting value of 109 +/- 4 mmHg, and heart rate 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, Beattie and Bresnahan scale. Histopathology of the
clip-compression lesion site in the cord consisted of extensive central
necrosis extending several segments rostral and caudal to the lesion. Quantitative measures of the small-diameter afferent arbors revealed significant increases in area ranging from 20-27% 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 afferent arbors and
autonomic dysreflexia. At 2 weeks after milder (20-g)
clip injury at T4, rats exhibited responses to colon distension that were not those associated with
autonomic dysreflexia (n = 5). Arterial pressure increased 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 cavitation within the gray matter. No change in the small-diameter afferent arbor was 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 are contributes to the development of
autonomic dysreflexia. Neither dysreflexia, nor changes in the afferent arbor size occurred after mild cord injury. This clinically relevant
clip compression cord injury model, studied more frequently for locomotor function, is excellent for investigating mechanisms for the development of
autonomic dysreflexia and strategies for its prevention.