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 by stimulation of sensory nerves in the body below the site of injury. Central sprouting of small-diameter primary afferent fibers in the dorsal horn of the spinal cord occurs concurrently with the development of this condition. We propose a model for the development of autonomic dysreflexia in which increased nerve growth factor (NGF) in the injured cord stimulates small-diameter primary afferent fiber sprouting, thereby magnifying spinal sympathetic reflexes and promoting dysreflexia. We identified this population of afferent neurons using immunocytochemistry for calcitonin gene-related peptide. Blocking intraspinal NGF with an intrathecally-delivered neutralizing antibody 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 induced by colon stimulation. The extent of small-diameter afferent sprouting after cord transection correlated significantly with the magnitude of increases in arterial pressure during the autonomic dysreflexia. Neutralizing NGF in the spinal cord is a promising strategy to minimize the life-threatening autonomic dysreflexia that develops after spinal cord injury.
Krenz
N R
NR
Neurodegeneration Research Group, The John P. Robarts Research Institute, The University of Western Ontario, London, Ontario, N6A 5K8 Canada.
Meakin
S O
SO
Krassioukov
A V
AV
Weaver
L C
LC
D000344:Afferent Pathways / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology; D009414:Nerve Growth Factors / Q000276:immunology / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
D000906:Antibodies; D007074:Immunoglobulin G; D009414:Nerve Growth Factors