Nerve growth factor administration protects against experimental diabetic sensory neuropathy.
Small fiber sensory neuropathy is one of the most common complications of diabetes mellitus. Currently there is no adequate therapy to prevent this often debilitating problem. Nerve growth factor (NGF) is a protein that promotes the survival and integrity of a large percentage of sensory neurons including the small fiber pain transmitting neurons which are often prominently affected in diabetic neuropathy. We report here that exogenously administered NGF is capable of preventing the behavioral and biochemical manifestations of diabetic sensory neuropathy in a streptozocin induced rat model. NGF administration prevented the elevation of tailflick threshold (a measure of the rat's response to a thermal noxious stimulus) which occurred in streptozocin-induced diabetic rats. Further, it prevented the induced reduction in levels of the neuropeptides substance P and calcitonin gene related peptide measured from cervical dorsal root ganglia. Finally, NGF did not ameliorate the prolonged latency of the compound action potentials measured from the caudal nerve of the tail. In view of these results, a clinical trial of NGF in diabetic neuropathy has now commenced.
Apfel
S C
SC
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Arezzo
J C
JC
Brownlee
M
M
Federoff
H
H
Kessler
J A
JA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D008297:Male; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism
D009414:Nerve Growth Factors; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide