From muscle spindles
From Golgi tendon organs
From Meissner’s and Pacinian corpuscles & endings in skin & connective tissue
From skin; pressure afferents
From skin; pain (pin-prick), temperature afferents
To skeletal muscles
To intrafusal fibers of muscle spindles
To pre-gangliononic autonomic efferents
To post-ganglionic autonomic efferents
Large myelinated fibers are preferentially tested by nerve conduction studies since their larger diameter (12–20 μm) axons allow these fibers to conduct the fastest of all motor fibers (70–120 m/s). Myelination of these axons further increases conduction velocity by enabling saltatory conduction which will be discussed in detail below. Myelin is produced by supportive Schwann cells that wrap or layer each axon in a fatty, protective spiral coat with numerous layers. Layering of myelin is seen quite nicely on electron microcopy (ultrastructure) of peripheral nerves (Fig. 2.1). The total thickness of myelin in a mature nerve is approximately 2/3 the diameter of the axon. Large myelinated fibers include: (1) afferent fibers from muscle spindles and Golgi tendon organs which relay important information about joint position and stretch which is critical for our reflexes as well as; (2) motor efferent fibers travelling from the motor neurons to skeletal muscles. Peripheral nerve myelination progresses significantly during the first few years of life as is reflected in the normal neonatal ulnar nerve motor conduction velocities of 20–35 m/s which increase to adult normal values (>50 m/s) by 3–5 years of age .
Ultrastructural image of a normal, large myelinated peripheral nerve (arrow head). The axon is seen in cross-section and has been wrapped in layers or spirals of protective myelin by the adjacent Schwann cell (arrow). Photo credit: Dr. Jean Michaud, Department of Pathology, Children’s Hospital of Eastern Ontario
Small myelinated fibers are approximately half the diameter of large fibers and not surprisingly conduct more slowly than their larger counterparts. Examples of small myelinated afferent fibers include axons extending from Meissner and Pacinian corpuscles. These are touch receptors located near the surface of the skin. When the corpuscle is deformed by pressure, the nerve endings are stimulated. They are well adapted to feeling rough surfaces and detecting vibration such that they respond to transient touch rather than sustained pressure. Small myelinated efferent fibers also supply the intrafusal fibers of muscle spindles as well as preganglionic autonomic efferents.
Small unmyelinated fibers are the smallest axons (<2 mm) and due to their extremely slow conduction velocity (<2 m/s) cannot be tested by conventional nerve conduction studies. Neurophysiologists must be aware of the limitations of testing such that when a small fiber neuropathy is suspected on clinical grounds, ancillary testing is considered as appropriate (see Chap. 19). Examples of small unmyelinated afferent fibers include sensory fibers carrying information regarding pain (pin-prick) and temperature sense. Small unmyelinated efferent fibers innervate post-ganglionic autonomic organs.
Each peripheral nerve fiber or axon is surrounded by multiple levels of connective tissue. Endoneurium surrounds individual axons. Individual axons are clustered into fascicles that are surrounded by a layer of connective tissue called perineurium. This in turn is surrounded by a thicker layer of epineurium that binds together multiple perineurial-bound fascicles as well as arterioles (Fig. 2.2).
Normal peripheral nerve sections stained with p-phenylenediamine at (a) high power shows large myelinated axons (diamond), small myelinated axons (square) and unmyelinated axons (circle) all surrounded by endoneurium; (b) medium power shows a fascicle containing many axons surrounded by perineurium (arrow head) which in turn is surrounded by epineurium (arrow); (c) low power demonstrates how the epineurium (arrow) binds together multiple fascicles and also contains arterioles. Photo credit: Dr. Gerard Jansen, Department of Pathology, The Ottawa Hospital Civic Campus
Signal transmission along peripheral nerves is based upon the presence of a stable electrochemical charge across the cell membrane of an axon, with a mechanism for rapid and reversible changes of that charge in response to stimuli.
The difference in electrochemical charge at baseline is referred to as a resting membrane potential. Ion pumps, typically requiring energy provided by adenosine triphosphate (ATP), are responsible for transporting ions such as Na+, K+, Cl− and Ca2+ into or out of the cell to establish electrical and chemical concentration gradients. Typically, resting membrane potentials of most glial cells is approximately −75 mV (i.e., the cytoplasm is negative compared to the extracellular matrix). Phospholipid bilayers are hydrophobic, thereby preventing charged particles from easily moving through membranes. Despite this, functional ion pumps are required to prevent ions from eventually diffusing across their electrochemical concentration gradients which would result in the loss of the resting membrane potential.
Ion channels are proteins that span cell membranes and can allow the passage of specific ions through an otherwise impermeable lipid bilayer. Specific factors can trigger a conformational change in ion channel proteins, causing them to open and permit the rapid influx or efflux of ions. Ion channels can be stimulated to open by; (1) binding with a ligand (i.e., a neurotransmitter); (2) local changes in voltage (i.e., propagation of an action potential); (3) local stress or pressure (i.e., common trigger for sensory mechanoreceptors) as well as; (4) phosphorylation which more typically results in prolonged configuration changes that can modulate the resting membrane potential.