Differential sensitivity of various types of nerve fibers to local anesthetics depends on fiber diameter, myelination, physiologic firing rate, and anatomic location. In general, smaller fibers are blocked more easily than larger fibers, and myelinated fibers are blocked more easily than unmyelinated fibers. Activated pain fibers fire rapidly; thus, pain sensation appears to be selectively blocked by local anesthetics. Fibers located in the periphery of a thick nerve bundle are blocked sooner than those in the core because they are exposed earlier to higher concentrations of the anesthetic.