High-frequency stimulation induces axonal conduction block without generating initial action potentials

The purpose of this modeling study is to develop a novel method to block nerve conduction by high frequency biphasic stimulation (HFBS) without generating initial action potentials. An axonal conduction model including both ion concentrations and membrane ion pumps is used to analyze the axonal response to 1 kHz HFBS. The intensity of HFBS is increased in multiple steps while maintaining the intensity at a sub-threshold level to avoid generating an action potential. Axonal conduction block by HFBS is defined as the failure of action potential propagation at the site of HFBS. The simulation analysis shows that step-increases in sub-threshold intensity during HFBS can successfully block axonal conduction without generating an initial response because the excitation threshold of the axon can be gradually increased by the sub-threshold HFBS. The mechanisms underlying the increase in excitation threshold involve changes in intracellular and extracellular sodium and potassium concentration, change in the resting potential, partial inactivation of the sodium channel and partial activation of the potassium channel by HFBS. When the excitation threshold reaches a sufficient level, an acute block occurs first and after additional sub-threshold HFBS it is followed by a post-stimulation block. This study indicates that step-increases in sub-threshold HFBS intensity induces a gradual increase in axonal excitation threshold that may allow HFBS to block nerve conduction without generating an initial response. If this finding is proven to be true in human, it will significantly impact clinical applications of HFBS to treat chronic pain.