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The role of endogenous nerve growth factor in human diabetic neuropathy

Abstract

Nerve growth factor (NCF) is trophic to sensory and sympathetic fibers1–3. In animal models, NGF is depleted in diabetic nerves4 and NGF deprivation produces hypoalgesia5. Exogenous NGF can reverse some of the pathological changes in diabetic nerves1,6 and NGF excess leads to hyperalgesia5. We have quantified sensory and autonomic function in early diabetic polyneuropathy and correlated changes with levels of NGF and neuropeptides in affected skin. We describe an early length–dependent dysfunction of sensory small–diameter fibers, prior to dysfunction of sympathetic fibers, with depletion of skin NGF and the sensory neuropeptide substance P. We describe a significant correlation between NGF depletion and decreased skin axon–reflex vasodilation, mediated by small sensory fibers partly via substance P release3. Immunostaining shows depletion of NGF in keratinocytes in diabetic skin. We propose that a decrease in endogenous skin–derived NGF influences the presentation of diabetic polyneuropathy, although metabolic or vascular abnormalites may be the cause of the neuropathy7,8. As loss of nociception and axon–reflex vasodilation contribute to diabetic foot ulceration9, early and prolonged NGF treatment at an appropriate dose may provide rational prophylaxis for this condition.

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Anand, P., Terenghi, G., Warner, G. et al. The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med 2, 703–707 (1996). https://doi.org/10.1038/nm0696-703

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