A nerve is a bundle of axons, the long, slender projections of nerve cells that transmit electrical signals throughout the body. When a nerve is cut, this connection is immediately severed, leading to a loss of function such as paralysis, loss of sensation, or both, depending on the nerve’s purpose. The possibility of successful repair depends heavily on the type of nerve and the severity of the damage. Restoration of function is a slow and challenging process requiring regenerating nerve fibers to accurately bridge the gap and reconnect with their original targets.
The Critical Distinction: Central vs. Peripheral Nerves
The success of nerve repair is determined by whether the injury occurred in the Central Nervous System (CNS)—the brain and spinal cord—or the Peripheral Nervous System (PNS). Nerves within the PNS possess an intrinsic ability to regenerate after injury, unlike those in the CNS, which generally cannot repair themselves spontaneously.
This difference is due to the distinct cellular environments surrounding the axons. In the PNS, specialized Schwann cells actively support and encourage regeneration. Conversely, the CNS environment is inhibitory toward axonal regrowth.
CNS axons are myelinated by oligodendrocytes, which express inhibitory proteins, such as Nogo-A, that prevent neurite outgrowth. Damage in the CNS also results in the formation of a glial scar, which acts as a physical and chemical barrier blocking the path of regenerating axons. The supportive structure of the PNS facilitates the repair process, making the injury location the most important factor for recovery.
The Natural Regeneration Process in Peripheral Nerves
When a peripheral nerve is severed, the axon section distal to the injury undergoes Wallerian degeneration, a prerequisite for successful regeneration. This active degeneration begins within 24 to 36 hours, involving the fragmentation of the axon’s skeleton and the breakdown of its myelin sheath. Macrophages and Schwann cells work together to clear this debris.
The Schwann cells, which originally produced the myelin, dedifferentiate and proliferate after the injury. They align themselves in organized structures called the bands of Büngner, which form tubes that act as a scaffold to guide the regenerating fibers across the injury site. The cell body of the injured neuron, located in the dorsal root ganglion or spinal cord, responds by upregulating genes required for growth and sending out multiple axonal sprouts from the proximal nerve stump.
These axonal sprouts, or growth cones, extend slowly along the guiding structures provided by the Schwann cells toward the distal segment. Regrowth typically advances at a pace of about 1 to 3 millimeters per day. Success hinges on one sprout finding and connecting with the correct endoneurial tube of the distal segment, allowing it to continue growth toward the original target muscle or sensory receptor.
Medical and Surgical Repair Techniques
For recovery, the two severed ends of a peripheral nerve must be brought together and aligned precisely, especially if the injury created a gap too wide for the axons to bridge naturally. When a clean cut results in a minimal gap, the preferred method is primary repair, or neurorrhaphy. This involves surgically suturing the outer layer of the nerve (epineurium) to hold the fascicle bundles in correct alignment without tension. Placing sutures under tension is avoided because it inhibits regeneration and leads to scarring.
If a segment of the nerve has been lost, creating a defect larger than a few millimeters, direct tension-free repair is not possible, and a bridging technique must be employed. The primary method for bridging larger gaps is the autologous nerve graft, where a segment of a less-critical sensory nerve, such as the sural nerve from the leg, is harvested and used to span the defect. The harvested graft acts as a biological scaffold, complete with supportive Schwann cells and endoneurial tubes, guiding the regenerating axons from the proximal to the distal stump.
As an alternative, nerve guidance conduits (tubes) are increasingly used, especially for shorter gaps (less than 3 centimeters). These can be synthetic or natural resorbable tubes that enclose the nerve ends, creating a protected microenvironment and preventing scar tissue interference. The conduit fills with fluid that supports a fibrin matrix, which then acts as a scaffold for the migrating Schwann cells and growing axons. For severe injuries where the proximal nerve segment is unavailable, a nerve transfer may be performed, rerouting a nearby functioning nerve to power the denervated target muscle.
Factors Influencing Recovery and Successful Function
Functional recovery after nerve repair is not guaranteed and is influenced by a combination of factors related to the patient, the injury, and the surgical intervention. Patient age is a significant variable, with younger individuals typically showing better results because their nervous systems are more plastic and their target muscles take longer to atrophy. The patient’s overall health, including the presence of comorbidities, also plays a role in the body’s healing capacity.
The nature and location of the injury profoundly affect the outcome. A clean laceration generally heals better than a crush or avulsion injury, which causes more widespread internal damage. Injuries located closer to the nerve’s cell body (proximal injuries) have a poorer prognosis because the regenerating axon must travel a much longer distance before reaching its target.
A long delay between injury and repair decreases the chance of a good outcome. This delay allows the denervated muscle to atrophy and the distal Schwann cells to lose their ability to support regeneration. Even with successful regeneration, full functional recovery is rare because axons may misroute to the wrong fascicle—for example, a motor axon growing down a sensory pathway—leading to incomplete or mixed functional return.