Rhythm transformation in nerve fibers by local anesthetics: From biophysics of sodium channels to physiology of anesthesia

The review considers the basic stages in the study of rhythm transformation in the nerve fibers by local anesthetics and underlying use-dependent block of sodium channels. A potency of use-dependent local anesthetics to produce the rhythm transformation in nociceptive nerve fibers sufficient to attain local anesthesia without complete block of conduction was examined. A hypothesis was tested on attaining the conditions of local anesthesia by a decrease in discharge frequency of C-fiber nociceptors below the critical level separating the firing frequency in these sensors corresponding to their excitation with subnociceptive and nociceptive chemical stimuli. This critical level (about 2 Hz) was determined by comparison of the discharges in feline cutaneous C-fiber nociceptors during injection of chemical nociceptive and non-nociceptive stimuli. The discharge frequency in C-fiber nociceptors can be decreased in a use-dependent manner below the critical level by subcutaneous injection of lidocaine or N-propyl-ajmaline. The importance of use-dependent local anesthesia for preservation of trophic influences of the nervous system in the damaged tissue is discussed.