Each neuron’s axon requires a continuous energy supply for impulse transmission and axonal transport. This is provided by an extrinsic vascular system and an intrinsic vascular system, which are interconnected. The extrinsic vessels enter the mesoneurium and communicate with the epineurial space via the vasa nervorum. A plexus develops at this level and runs longitudinally (Fig. 9.6). If the fascicles are examined closely, a large number of epineurial vascular branching is seen, supplying each fascicle in a segmental manner, so that each fascicle is vascularly analogous to a complete axon in a miniature model.

The vascular plexus enters the endoneurium through the perineurium at an oblique angle to anastomose with the intrinsic circulation that surrounds each fascicle. The oblique passage of vessels through the inner perineurial membrane is a site of potential circulatory compromise within the intrafascicular tissue.

A neuron consists of a nerve cell body and its ­processes. There are a number of dendrites associated with the cell body and one long extension – an axon, which travels to an end organ with branches terminating in peripheral synaptic terminals. Nerve fibers can be either myelinated or unmyelinated. Sensory and motor nerves contain both types of fibers in a ratio of 4 unmyelinated axons to 1 myelinated axon.

Unmyelinated fibers are made up of several axons enclosed by a single Schwann cell (Fig. 9.7). Unmyelinated axons are small in diameter, usually averaging 0.15–2.0 μm. The axons of a myelinated fiber are individually wrapped by a single Schwann cell that has laid down a laminar myelin sheath (Fig. 9.8). The center of a myelinated fiber is made up of cytoplasm (axoplasm) with associated cytoskeletal elements surrounded by a ­membrane (axolemma). A concentric sheath of myelin and a Schwann cell surround this ­membrane (Fig. 9.9). A thin basal lamina invests the interdigitating processes of Schwann cells. At the ­junction between two Schwann cells, the axolemma becomes exposed at a gap called a node of Ranvier (Fig. 9.10). The propagation of an action potential along the axon “jumps” from node to node over the insulated areas covered with myelin in the process of saltatory conduction. This provides for more rapid propagation along the axon. As a result, myelinated fibers are able to conduct an impulse at a speed up to 150 m/s, while unmyelinated fibers propagate impulses at speeds of 2–2.5 m/s.

The cell bodies of the peripheral trigeminal nerve, including the lingual and inferior alveolar nerve, are contained within the trigeminal ganglion (also called the semilunar ganglion). The trigeminal ganglion is analogous to the dorsal root ganglia of the spinal cord, which contain the cell bodies of incoming sensory fibers from the rest of the body. These nerve cells may have axons that extend over a distance corresponding to thousands of cell body diameters. This imposes special requirements on the communication systems between the proximal and distal regions of the cell. To meet these requirements the neuron has unique systems of anterograde as well as retrograde intracellular transport. These transport mechanisms are involved in the response to an injury.

Clinically useful injury grading systems have been developed that allow reflection of patient symptomatology after nerve injury and with the histological changes occurring to the nerve. Histological parameters are the far most used predictors of peripheral nerve damage and regeneration. In 1941, Cohen introduced a classification scheme to describe the injury to peripheral nerves: neuropraxia, axonotmesis, and neurotmesis [30]. In the early 1940s, Seddon [33] examined 650 patients with peripheral injuries and popularized Cohen’s time and degree of recovery-based classification system. In 1951, Sunderland [36] expanded upon this classification system by defining five distinct degrees of nerve injury based on histological changes within the nerve [30] (Figs. 9.11 and 9.12). Within this classification scheme, first-degree injuries are representative of a neuropraxia, while axonotmesis is divided into second-, third-, and fourth-degree injuries. Fifth-degree injuries represent a neurotmesis. In 1989, Mackinnon coined the term “Sixth-degree injury” which was defined as a mixed injury involving different combinations of the above [29].

The healing of peripheral nerve injuries is quite unique within the body as it is a process of cellular repair rather than tissue repair. In other words, the nerve cells themselves do not undergo mitoses. The number of nerve cells (neurons) does not increase, but the amputated nerve cell regains its original axoplasmic volume by sending out new processes to the end organ target. Peripheral nerves do have this capacity to regrow, but functional recovery in humans is often incomplete [15]. This is because the neuron and surrounding cells cannot maintain an effective growth promoting response for long periods of time. Peripheral nerves are some of the longest and most spatially complex cells in the body. A normal, uninjured nerve is represented in Fig. 9.13. Their length makes them unable to function without the structural and metabolic support provided by approximately ten times as many glial support cells [20]. A nerve injury that takes place centimeters from a neuronal cell body induces a response that involves the entire cell and its associated glial support cells. Although the number of neurons does not increase in number, the repair of each cell takes place in an environment of intense cellular proliferation. The cells that do show evidence of proliferation include Schwann cells, endothelial cells, and fibroblasts.