Integrative action of axonal membrane explored by trains of subthreshold stimuli applied to the peripheral nerve

The objective of this study was to provide evidence on the integrative action of axonal membrane in humans and its ability to integrate multipulse subthreshold stimuli and generate action potential.

The median nerve was stimulated at the wrist in six healthy subjects and 17 patients who underwent low spine surgery by means of percutaneous electrodes, with trains of one to nine near-threshold constant-current stimuli of 500-μs duration. The interstimulus interval between stimuli was 2 or 4 ms. The compound muscle action potential (CMAP) was recorded from the abductor pollicis brevis muscle using subcutaneous needle electrodes in patients and surface electrodes in healthy subjects. Total intravenous anesthesia (TIVA) without a muscle relaxant was used in all patients, and measurements were performed at the end of surgery.

A single near-threshold stimulus did not generate CMAP either in the healthy subjects or in the patients. However, when the number of near-threshold stimuli was increased to two to nine stimuli, and packed into a short train with interstimulus intervals of 2 or 4 ms, a CMAP of varying amplitude from 100 to 200 μV was successfully elicited.

We concluded that the described phenomenon might be explained by the integrative action of the axonal membrane, which is able to summate the trains of subthreshold stimuli, increasing the resting potential to the firing level, and consequently generating CMAP. This is because the subthreshold stimuli make the axonal membrane hyperexcitable.

This phenomenon is not very well explored in clinical neurophysiology, and it needs to be studied further. This can explain some neurophysiologic phenomena during intraoperative monitoring.