Authors: Ward RJ, Benveniste RJ.
Title: Nerve conduction and the effect of local anesthesia.
Journal: J Oral Ther Pharmacol
Date: Jan 1968
Citation: 4(4):292-7
Category: Endodontic Pharmacology
Evidence-based Ranking: 5
Purpose/Objectives: To discuss the mechanisms by which the nerve impulse is propagated and the effects of local anesthetics on these mechanisms. Discussion: This paper first discusses the anatomy of the nerve, with the nerve membrane being sandwiched between two lipid layers. Since lipids do not absorb water, water and water-soluble substances cannot easily penetrate the membrane. Two basic types of nerve fibers exist in vertebrates, myelinated and unmyelinated. In myelinated nerves, a sheath of myelin surrounds the nerve fiber and acts as an insulator. This sheath is interrupted at intervals of approximately 2 mm along the fiber by indentations called nodes of Ranvier. The peripheral nerve is made up of many fibers which can be subdivided into three groups, A, B and C fibers. A and B fibers are myelinated and C fibers are unmyelinated. It is theorized that because ions and some other substances can traverse the cell membrane, that the membrane is perforated. The resting membrane is 100 times more permeable to the K+ ion than to the Na+ ion. It is believed that the pores or perforations in the membrane are large enough for the K+ ions (2.2 angstroms) to pass but too small for the Na+ ions (3.4 angstroms) to pass readily. At rest, the concentration of K+ is about 30 times higher in the intracellular than in the interstitial fluid and that the Na+ concentration is higher in the extracellular fluid. Because of the ionic gradients of Na+ and K+, the interstitial border becomes positively charged and the intracellular border becomes negatively charged, creating a transmembrane voltage of -90 mV. The resting nerve membrane is considered to be polarized. Although Na+ is relatively unable to cross the membrane, some enters the cell because of the negatively charged intracellular fluid. The cell uses a sodium pump to extrude the Na+ to keep the intracellular Na+ at a low level. When nerve cells are stimulated, there is a brief change in ionic permeability of the membrane which allows an increase of Na+ ions to enter the cell. Electrically this causes a depolarization at a rapid rate which gives rise to an action potential. The sodium pump restores equilibrium and repolarization. Local anesthetics, which exist as bases or salts, dissociate when injected into tissue, and are absorbed into the membrane. The LA molecule occupies the receptor site, thus hindering Na+ access to the membrane. This prevents depolarization and the resting potential of the membrane remains unchanged which makes impulse propagation impossible.

Summary: Nerve conduction is basically a process of propagating an impulse from the site of stimulation to other regions. This is accomplished because the nerve membrane is an excitable structure which is polarized in the resting state. Stimulation of the nerve leads to depolarization, which alters ionic permeability. These membrane changes are then transmitted to adjacent regions. Local anesthetics are amines, which are supplied in the salt form, but whose mechanism of action is dependent upon the conversion to the base form in the tissues. The anesthetic agent is adsorbed on the nerve membrane and prevents impulse transmission by blocking Na++ entry. Depolarization of the membrane is thus prevented, and the impulse is blocked. ReviewerÂ’s Comments: This paper is a good overall summary of nerve anatomy and physiology and how local anesthetic works.