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A better understanding of some features of the fine structure of peripheral nerves may provide us with essential information that can be helpful in anesthetic clinical practice. This chapter reviews the ultrastructure of connective tissues of peripheral nerves to facilitate understanding of its role as the perineurial diffusion barrier and implication in regional anesthesia.


Nerves and their principal branches (Figures 5–1, 5–2, 5–3) consist of parallel bundles of nerve fibers (nerve fascicles, fasciculi). The size, number, and pattern of fasciculi vary among nerves and at different distances from their origin. When the connective tissue of the peripheral nerve is removed, 20 or more tubular structures or fascicles are typically seen.

Figure 5–1.

Sciatic nerve at the level of popliteal fossa. Scanning electron microscopy. Magnification ×25. (Reproduced with permission from Reina MA, Arriazu R, Collier CB, et al: Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data, Rev Esp Anestesiol Reanim. Dec 2013;60(10):552-562.)

Figure 5–2.

Scanning electron microscopy image of the human tibial nerve fascicles and adipose tissue that between fascicles. Magnification ×75. (Reproduced with permission from Wikinski J, Reina MA, Bollini C, et al: Diagnóstico, prevención y tratamiento de las complicaciones neurológicas asociadas con la anestesia regional periférica y central. Buenos Aires: Panamericana Ed; 2011.)

Figure 5–3.

Sciatic nerve at the level of popliteal fossa. Hematoxylin-eosin. (Reproduced with permission from Reina MA, De Andres JA, Hernández JM, et al: Successive changes in extraneural structures from the subarachnoid nerve roots to the peripheral nerve, influencing anesthetic block, and treatment of acute postoperative pain. Eur J Pain. Suppl 2011;5(2):377-385.)

Inside each nerve, the axons form an intraneural plexus in such a fashion that one axon can contribute to different fascicles along the nerve length (Figure 5–4). In other words, an axon can travel from a peripheral position to a more central position as well as swap the fascicles altogether along its descent more peripherally.1,2,3,4 Indeed, cross-sectional anatomy of nerves at close distance from each other demonstrates that the location and number of fascicles within nerves are highly variable (see Figure 5–3) with the presence of intraneural plexuses (Figures 5–5 and 5–6). The number, size, and location of fascicles in peripheral nerves are also variable even within a single nerve and can vary as much as 23 times along a 4- to 5-cm length of nerve.5,6,7,8

Figure 5–4.

Diagram of intraneural plexus enclosed in a peripheral nerve. ...

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