Local anesthetics (LAs) primarily exert their pharmacological action at the nerve membrane, which serves as the critical site for their effect. The primary target of local anesthetics within this membrane is the sodium ion channels, essential components of nerve cells that regulate the flow of sodium ions during nerve impulses. When these channels are inhibited, the transmission of pain signals from the nerve endings to the brain is blocked, resulting in a loss of sensation.
Over the years, several theories have been proposed to explain the mechanism of action of local anesthetics at the nerve membrane. Earlier theories, such as the acetylcholine theory and the calcium displacement theory, have been largely discredited. The acetylcholine theory suggested that acetylcholine, a neurotransmitter involved in synaptic transmission, played a role in nerve conduction along the neuron body, but no evidence supports this in the context of nerve signal transmission. The calcium displacement theory suggests that local anesthetics exert their action by displacing calcium ions from the nerve membrane, thus altering its permeability to sodium ions. However, studies demonstrating that varying the concentration of calcium ions does not influence the efficacy of local anesthetics have diminished this theory’s credibility.
Another theory, known as the surface charge theory, proposed that local anesthetics bind to the nerve membrane and change its electrical potential, making the membrane less excitable. The idea was that the positive charge of the anesthetic molecules altered the membrane surface potential, raising the threshold for nerve excitation. However, this theory could not explain the effects of uncharged anesthetics like benzocaine, nor has it been supported by evidence that anesthetics act within the membrane channels rather than at the surface.
