Neutralizing intraspinal nerve growth factor blocks autonomic dysreflexia caused by spinal cord injury

Autonomic dysreflexia is a condition that develops after spinal cord injury in which potentially life-threatening episodic hypertension is triggered b y stimulation of sensory nerves in the body below the site of injury. Centr al sprouting of small-diameter primary afferent fibers in the dorsal horn o f the spinal cord occurs concurrently with the development of this conditio n. We propose a model for the development of autonomic dysreflexia in which increased nerve growth factor (NGF) in the injured cord stimulates small-d iameter primary afferent fiber sprouting, thereby magnifying spinal sympath etic reflexes and promoting dysreflexia. We identified this population of a fferent neurons using immunocytochemistry for calcitonin gene-related pepti de. Blocking intraspinal NGF with an intrathecally-delivered neutralizing a ntibody to NGF prevented small-diameter afferent sprouting in rats 2 weeks after a high thoracic spinal cord transection. In the same rats, this anti- NGF antibody treatment significantly decreased (by 43%) the hypertension in duced by colon stimulation. The extent of small-diameter afferent sprouting after cord transection correlated significantly with the magnitude of incr eases in arterial pressure during the autonomic dysreflexia. Neutralizing N GF in the spinal cord is a promising strategy to minimize the life-threaten ing autonomic dysreflexia that develops after spinal cord injury.