title: Autonomic dysreflexia and primary afferent sprouting after clip-compression injury of the rat spinal cord.
abstract: 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.
authors.affiliation: The John P. Robarts Research Institute and Department of Physiology University of Western Ontario, London, Canada. lcweaver@rri.on.ca
authors.forename: L C
authors.initials: LC
authors.lastname: Weaver
authors.forename: P
authors.initials: P
authors.lastname: Verghese
authors.forename: J C
authors.initials: JC
authors.lastname: Bruce
authors.forename: M G
authors.initials: MG
authors.lastname: Fehlings
authors.forename: N R
authors.initials: NR
authors.lastname: Krenz
authors.forename: D R
authors.initials: DR
authors.lastname: Marsh
mesh_terms: D000818:Animals; D020211:Autonomic Dysreflexia / Q000209:etiology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004396:Coloring Agents; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009475:Neurons, Afferent / Q000473:pathology*; D020671:Posterior Horn Cells / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D004396:Coloring Agents; D015740:Calcitonin Gene-Related Peptide