ANATOMY OF THE PERIPHERAL NERVE

Each peripheral nerve axon possesses its own cell membrane, the axolemma. Nonmyelinated nerves, such as autonomic postganglionic efferent and nociceptive afferent C fibers, contain many axons encased in a single Schwann cell sheath. Most large motor and sensory fibers are enclosed in many layers of myelin, which consists of plasma membranes of specialized Schwann cells that wrap themselves around the axon during axonal outgrowth. Myelin greatly increases the speed of nerve conduction by insulating the axolemma from the surrounding conducting salt medium and forcing the action current to flow through the axoplasm to the nodes of Ranvier, which are periodic interruptions in the myelin sheath where action currents are regenerated ( Fig. 14-3 ). The Na⁺ channels that serve impulse generation and propagation are highly concentrated at the nodes of Ranvier of myelinated fibers,^[7] but they are distributed all along the axon of nonmyelinated fibers ( Fig. 14-3 ). A classification of peripheral nerves according to fiber size and physiologic properties is presented in Table 14-3 .

A typical peripheral nerve consists of several axon bundles, or fascicles. Each fiber has its own connective tissue covering, the endoneurium. Each fascicle of axons is encased by a second connective tissue layer, the epithelial-like perineurium, and the entire nerve is wrapped in a loose outer sheath called the epineurium ( Fig. 14-4 ). To reach its site of action (the nerve axon), a local anesthetic molecule must traverse four or five layers of connective tissue or lipid membranous barriers, or both.

Structure of the Axonal Membrane

Biologic membranes consist of a molecular lipid bilayer containing proteins adsorbed on the surface, as well as embedded in or spanning the hydrocarbon core ( Fig. 14-5 ). The bilayer character is imposed by the amphiphilic phospholipids, which have long hydrophobic fatty acyl tails that lie in the center of the membrane, and polar hydrophilic head groups composed of zwitterionic

Figure 14-3 Pattern of "local circuit currents" flowing during impulse propagation in a nonmyelinated C fiber's axon (A) and a myelinated axon (B). During propagation of impulses, from left to right, current entering the axon at the initial rising phase of the impulse (gray downpointing arrows) passes through the axoplasm (local circuit current, red loops) and depolarizes the adjacent membrane. Plus and minus signs adjacent to the axon membrane indicate the polarization state of the axon membrane: negative inside at rest, positive inside during active depolarization under the action potential, and less negative in the regions where local circuit currents flow. This ionic current passes relatively uniformly across a nonmyelinated axon, but in a myelinated axon it is restricted to entry at the nodes of Ranvier, several of which are simultaneously depolarized during a single action potential.

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A dynamic interaction exists between the cell's membrane and cytoplasm. Although we focus here on the channel-blocking actions of local anesthetics, it is noteworthy that many other cellular activities, including both metabolic and signal transduction pathways, are inhibited by these drugs.

Figure 14-4 Transverse sections of a peripheral nerve (A) showing the outermost epineurium; the inner perineurium, which collects nerve axons in fascicles; and the endoneurium, which surrounds each myelinated fiber. Each myelinated axon (B) is encased in the multiple membranous wrappings of myelin formed by one Schwann cell, each of which stretches longitudinally over approximately 100 times the diameter of the axon. The narrow span of axon between these myelinated segments, the node of Ranvier, contains the ion channels that support action potentials. Nonmyelinated fibers (C) are enclosed in bundles of 5 to 10 axons by a chain of Schwann cells that tightly embrace each axon with but one layer of membrane.