Neurotrophins and peripheral neuropathy

Area of Science:

• Neuroscience
• Endocrinology
• Dermatology

Background:

• Peripheral neuropathies, including those from nerve trauma, diabetes mellitus, and leprosy, are common causes of nerve dysfunction.
• Nerve growth factor (NGF) plays a crucial role in nerve health and function.
• Understanding NGF levels in different neuropathies is essential for developing effective treatments.

Purpose of the Study:

• To investigate endogenous nerve growth factor (NGF) levels in patients with peripheral neuropathies.
• To correlate NGF levels with specific nerve fiber dysfunction and clinical manifestations.
• To explore the potential therapeutic role of NGF in managing neuropathies and their complications.

Main Methods:

• Measurement of endogenous NGF levels in patients with nerve trauma, diabetes mellitus, and leprosy.
• Assessment of small-diameter sensory fiber function, including axon-reflex vasodilatation.
• Immunostaining of NGF in skin and nerve tissues.
• Correlation analysis between NGF levels, neuropeptide substance P, and physiological responses.

Main Results:

• Diabetic neuropathy showed early dysfunction of small sensory fibers with depleted skin NGF and substance P, correlating with reduced axon-reflex vasodilatation.
• NGF was depleted in keratinocytes of diabetic skin and decreased in injured nerves and leprosy-affected tissues.
• NGF-immunostaining was observed in Schwann cells in distal nerve segments and neuromas.

Conclusions:

• Reduced NGF levels are a significant feature of peripheral neuropathies in diabetes and leprosy.
• Loss of nociception and impaired axon-reflex vasodilatation, linked to NGF depletion, may contribute to serious complications like skin ulceration.
• NGF holds potential as a prophylactic agent against ulceration in human neuropathies.