WS4.3. Overview of Axonal Excitability Studies

Abstract

Nerve excitability testing is a non-invasive neurophysiological technique, which investigates nerve functions in vivo . While nerve conduction studies deliver supramaximal stimuli to measure conduction velocities and the number of large myelinated fibres, nerve excitability studies use weaker stimuli and measure strength of stimuli, which evoke target compound muscle action potential or sensory nerve action potential amplitudes. The combination of conditioning and test stimuli, with various strength and duration, can examine functions of various types of ion channels and ion pumps and exchangers, which are located in peripheral nerve axons, and membrane potential. Several paradigms, such as strength-duration properties, threshold electrotonus, current-threshold relationship and recovery cycle, are assessed in this testing, and alterations of parameters in these paradigms indicate changes in those functions. This technique has disclosed various pathophysiological alterations mainly in genetic and acquired channelopathies. A famous study, using this technique, disclosed an effect of puffer fish poisoning for nerve excitability. Tetrodotoxin is known to block sodium channels, and salient reductions of strength-duration time constant and refractoriness in recovery cycle, makers of persistent and transient sodium channel functions, respectively, were disclosed in patients with tetrodotoxin intoxation. This study firstly visualized an effect of tetrodotoxin for the human peripheral nerve. In another study, increased strength-duration time constant, i.e. increased excitability, was revealed in patients with neuropathic pain and muscle cramps. Mexiletine treatment, a sodium channel blocker, for these patients relieved those symptoms and decreased strength-duration time constant. As those studies, recent studies, using this testing, have disclosed an impact of altered ion channel functions for neurological diseases and utility of this technique as a treatment biomarker. In this session, I plan to introduce the principle of this testing and recent advances in clarification of pathophysiology in neurological diseases and treatment developments, using this testing.