Nitric oxide in damage, disease and repair of the peripheral nervous system

Peripheral nerves provide essential connections between the central nervous system and muscles, autonomic structures and sensory organs. Nitric oxide (NO) participates in critical actions involving several aspects of peripheral nerve function and disease. It offers important roles in "normal" afferent signaling of pain through the dorsal horn of the spinal cord and in autonomic control through nitrergic innervation. NO is generated during the fundamental processes of Wallerian degeneration of peripheral nerves following injury that bear on subsequent regenerative events. Through its actions on vasa nervorum, the blood supply to nerves, NO participates in microvascular changes following injury but also has direct roles in axon and myelin breakdown and "clearance" prior to regeneration. During such processes, NO contributes to the development of neuropathic pain. Excessive local levels of NO during inflammation may damage axons and growth cones. Low-grade chronic rises in NO may also contribute toward peripheral nerve damage, or neuropathy in diabetes. In this review, we consider the evidence for these roles and their potential importance in disease and repair of peripheral nerves.