Reinnervation

Reinnervation is the process by which nerve fibers reestablish functional connections with their target tissues after injury or disease. In the peripheral nervous system, reinnervation typically involves regrowth of axons from the proximal stump, sprouting from nearby intact nerves, or the use of nerve grafts or nerve transfers to reach denervated muscles or sensory receptors. Successful reinnervation is a major determinant of functional recovery following nerve injury; in the central nervous system, plastic changes can modify how reinnervation signals are integrated.

Mechanistically, the process begins with Wallerian degeneration of the distal stump, followed by proliferation of Schwann cells and the formation of guidance pathways known as bands of Büngner. Regenerating axons grow along endoneurial tubes toward their targets, guided by neurotrophic factors and extracellular matrix cues. Growth occurs slowly, typically around 1 millimeter per day in humans, and accurate reinnervation of the correct motor or sensory target is essential; misrouting can produce synkinesis or faded function.

Clinically, outcomes depend on injury type and timing. Neurapraxia often recovers without intervention, whereas axonotmesis or more severe injuries may require surgical repair. Approaches include direct end-to-end neurorrhaphy, autologous nerve grafts, or nerve transfers (neurotization) to reroute intact donor axons to recipient muscles or sensory areas. Conduits, scaffolds, and adjuvant therapies such as electrical stimulation or rehabilitation programs may enhance regrowth and functional recovery.

Reinnervation in the central nervous system relies on cortical and subcortical plasticity to interpret new connections, while peripheral reinnervation success depends on distance to target, age, comorbidities, and the precision of axonal targeting. Even with reinnervation, functional outcomes may be partial and subject to maladaptive reorganization.