Local Anesthetics: Differential Sensitivity of Nerve Fibers

A local anesthetic, or LA, can block conduction in all nerves, not just the ones around the target site. The variable response of nerve fibers to the LA, or their differential sensitivity, restricts the anesthesia to a limited region.

Nerve fibers proximal to the injection site are blocked first, followed by the distal ones. Additionally, structural variations in neurons also contribute to their differential sensitivity.

Typically, neurons can be myelinated or unmyelinated. In myelinated neurons, the axons are surrounded by multilayered myelin sheaths interspersed with unmyelinated gaps or nodes of Ranvier. 

Differential nerve blockades depend on node spacing, myelination, or nerve type differences.

For example, narrow myelinated fibers with short internodal distances are more susceptible to LAs and are blocked faster than thicker fibers.

LA susceptibility also differs between sensory and motor neurons.

At low LA concentrations, sensory neurons are blocked first, while motor neurons remain unaffected. Such a differential blockade helps relieve pain during labor and delivery.