At a pH equal to the protonated bases pKa, the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equimolar amounts, but only the unprotonated base diffuses readily across cell membranes. Once inside the cell, the local anesthetic will be in equilibrium, with the formation of the protonated (ionized) form, which does not readily pass back out of the cell. This is referred to as "ion-trapping". In the protonated form, the molecule binds to the LA binding site on the inside of the ion channel near the cytoplasmic end. Most LAs work on the internal surface of the membrane - the drug has to penetrate the cell membrane, which is achieved best in the nonionised form. This is exemplified by the permanently ionised LA RAC 421-II which cannot diffuse across the cell membrane but, if injected into the cytosol of a nerve fibre, can induce NaKATPase blockage and anaesthetic effects. Acidosis such as caused by inflammation at a wound partly reduces the action of LAs. This is partly because most of the anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel. All nerve fibers are sensitive to LAs, but due to a combination of diameter and myelination, fibers have different sensitivities to LA blockade, termed differential blockade. Type B fibers (sympathetic tone) are the most sensitive followed by type C (pain), type A delta (temperature), type A gamma (proprioception), type A beta (sensory touch and pressure), and type A alpha (motor).
Although type B fibers are thicker than type C fibers, they are myelinated, thus are blocked before the unmyelinated, thin C fiber. Techniques
Local anesthetics can block almost every nerve between the peripheral nerve endings and the central nervous system. The most peripheral technique is topical anesthesia to the skin or other body surface. Small and large peripheral nerves can be anesthetized individually (peripheral nerve block) or in anatomic nerve bundles (plexus anesthesia). Spinal anesthesia and epidural anesthesia merge into the central nervous system. Injection of LAs is often painful. A number of methods can be used to decrease this pain, including buffering of the solution with bicarbonate and warming.Clinical techniques include:

Surface anesthesia is the application of an LA spray, solution, or cream to the skin or a mucous membrane; the effect is short lasting and is limited to the area of contact. Infiltration anesthesia is infiltration of LA into the tissue to be anesthetized; surface and infiltration anesthesia are collectively topical anesthesia
Field block is subcutaneous injection of an LA in an area bordering on the field to be anesthetized. Peripheral nerve block is injection of LA in the vicinity of a peripheral nerve to anesthetize that nerves area of innervation. Plexus anesthesia  is injection of LA in the vicinity of a nerve plexus, often inside a tissue compartment that limits the diffusion of the drug away from the intended site of action. The anesthetic effect extends to the innervation areas of several or all nerves stemming from the plexus.