Peripheral Nerve Response to Injury

Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

Injury to the peripheral trigeminal nerve results in various extents of nerve fiber injury. The consequences to the patient are almost always detrimental and can influence the patient’s ability to eat comfortably, taste, manage oral secretions, and speak clearly. Many lingual and inferior alveolar nerve injuries require no surgical intervention and the patient’s sensation returns to normal with time. Other injuries show incomplete or no improvement with time. To compare these 2 types of clinical scenarios, the surgeon must first understand the response of the peripheral nerve to injury. The fate of the axons and/or the surrounding architecture of the nerve components is critical for recovery after injury. The healing of nerve injuries is unique within the body because it is a process of cellular repair rather than cell division or mitosis. The nerve cells at the site do not increase in number after an injury, but attempt to restore the axoplasmic volume and continuity of the original neurons.


A sophisticated understanding of the anatomy of the peripheral nerve is beneficial to comprehending the series of events that takes place after an injury. A normal polyfascicular trigeminal nerve is shown in Fig. 1 . The components of the peripheral nerve include connective tissue, blood vessels, and the basic unit of the peripheral nerve: an axon and its associated Schwann cells. The nerve trunk represents a composite tissue constructed for the purpose of maintaining continuity, nutrition, and protection of these basic units, which require a continuous energy supply to allow for impulse conductivity and axonal transport.

Fig. 1
Cross-sectional view of the peripheral trigeminal nerve internal anatomy.
( Courtesy of Don Johnson, Emory University, Atlanta, GA.)

Connective Tissue

The connective tissue subdivisions provide the framework around and within the nerve. The resulting architecture consists of an external and internal epineurium, and a perineurium surrounding each fascicle, in which are contained multiple axons surrounded by endoneurium. A fourth subdivision includes a mesoneurium that consists of loose areolar tissue continuous with the epineurium and the surrounding tissue bed. The mesoneurium allows the nerve to move a certain distance longitudinally within the surrounding tissue.

The outer connective tissue layer of the nerve is the external epineurium, which is a supporting and protective connective tissue made up primarily of collagen and elastic fibers ( Fig. 2 ). The internal epineurium is the structure that invests the fascicles, which contain the nerve fibers. Usually, several fascicles are grouped together in bundles, constituting well-defined subunits of the nerve trunk. Fascicles vary in size and quantity depending primarily on whether the region in question is at the proximal or distal site of the nerve. Both the lingual and inferior alveolar nerves are polyfascicular. The lingual nerve contains 15 to 18 fascicles at the region adjacent the mandibular third molar, whereas the inferior alveolar nerve contains 18 to 21 fascicles within the angle of the mandible.

Fig. 2
Light micrograph of a peripheral nerve in transverse section. Several fascicles that make up this nerve are enveloped by the connective tissue of the epineurium (Ep) that merges imperceptibly with the surrounding loose connective tissue, the mesoneurium. A more deeply stained perineurium (Pe) encloses the fascicles. Each fascicle consists of a large number of nerve fibers that are embedded in a more delicate endoneurium (not well defined at this level of magnification). Magnification ×200, Masson trichrome.
( From Netter illustration from . © Elsevier Inc. All rights reserved.)

Each fascicle is surrounded by perineurium, a lamellated sheath with considerable tensile mechanical strength and elasticity ( Fig. 3 ). The perineurium is made up of collagen fibers dispersed among perineural cells and acts as a diffusion barrier as a result of its selective permeability, separating the endoneurial space within it from the surrounding tissues. This separation preserves the ionic environment within the fascicle.

Fig. 3
Light micrograph of a nerve fascicle at higher magnification. The perineurium (Pe) is dark blue and the endoneurium (EN) light blue. Nerve fibers (NF) are densely stained structures surrounded by a myelin sheath (MS), which is red. A capillary (Cap) is shown. Magnification ×465, Masson trichrome.
( From Netter illustration from . © Elsevier Inc. All rights reserved.)

The nerve fibers are closely packed within endoneurial connective tissue (endoneurium) inside each fascicle ( Figs. 4 and 5 ). The endoneurium is composed of a loose gelatinous collagen matrix.

Fig. 4
( A ) Light micrograph of a peripheral nerve fascicle in transverse section. Osmium fixation shows well-preserved myelin sheaths of nerve fibers. Nerve fibers vary in diameter, and perineurium surrounds the fascicle (To luidine blue, magnification ×600; semithin plastic section). ( B ) Electron micrograph of a myelinated nerve fiber and its associated Schwann cell in transverse section. The myelinated nerve fibre axoplasm (Ax) contains cytoskeletal elements and mitochondria that parallel its long axis. The Schwann cell, sectioned at the level of its nucleus, is enveloped externally by a basal lamina. Flattened perineurial cells (Pe) and collagen fibrils of the endoneurium (En) are also seen (magnification ×16,800).

Fig. 5
Light micrograph of peripheral nerve in longitudinal section. Nerve fibers (NF), the slender deeply stained threads, pursue a wavy course. Myelin sheaths (MS) appear vacuolated because of high lipid content and the effects of paraffin embedding on the tissue sample. Schwann cells (SC) have elongated nuclei. They are indistinguishable from the nuclei of fibroblasts of the delicate endoneurium (En) that invests the individual nerve fibers. A deeply stained perineurium (Pe) surrounds the nerve fascicle externally. Magnification ×700, hematoxylin-eosin.
( From Netter illustration from . © Elsevier Inc. All rights reserved.)

Blood Supply

The axon of each neuron requires a continuous energy supply for impulse transmission and axonal transport. This energy is provided by extrinsic and an intrinsic vascular systems, 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. 6 ). Close examination of the fascicles reveals a large number of epineurial vascular branches, supplying each fascicle in a segmental manner, so that each fascicle is vascularly analogous to a complete axon ( Fig. 7 top).

Fig. 6
A lingual nerve under microscopic magnification showing the vasa nervorum (VN). Large longitudinally oriented intrinsic epineurial arteriolar and venular vessels can be seen deep to this plexus.

Fig. 7
Anatomy of a peripheral nerve. Both the interconnected (intrinsic) vascular components and the nerve fiber types (myelinated and unmyelinated) are shown. Vessels are abundant in all layers of the nerve, forming a pattern of longitudinally oriented vessels. Vessels penetrate the perineurium following an oblique course. Myelinated and unmyelinated axons are shown ( bottom ). A single Schwann cell can envelop multiple unmyelinated axons and concentrically wrap its cell membrane around an axon to form a myelinated fiber.
( From Netter illustration from . © Elsevier Inc. All rights reserved.)

The 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.

Nerve Fibers

A neuron consists of a nerve cell body and its processes. There are several dendrites associated with the cell body and 1 long extension: an axon that travels to an end organ with branches terminating in peripheral synaptic terminals.

Nerve fibers can be either myelinated or unmyelinated (see Fig. 7 bottom). Sensory and motor nerves contain both types of fibers in a ratio of 4 unmyelinated to 1 myelinated.

Unmyelinated fibers are made up of several axons enclosed by a single Schwann cell ( Fig. 8 ). Unmyelinated axons are small in diameter, usually averaging 0.15 to 2.0 μm.

Jan 23, 2017 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Peripheral Nerve Response to Injury
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