Effects of subthreshold stimuli on the excitability of axonal membrane

8.1

Introduction

The action potential, initiated by the depolarization of the axonal membrane, has classically been described as having periods of both hypo- and hyperexcitability . Historically, most investigations related to axonal excitability use paired stimuli by first applying a test stimulation pulse (usually of suprathreshold intensity) and then a conditioning stimulus pulse (a percentage of that test stimulus) .

Bostock and Trevillion have described that subthreshold or near threshold electrical stimuli applied to a peripheral nerve can cause an increase in axonal excitability . This effect is very well known, but it still constitutes the poorly understood phenomenon of the integrative action of peripheral nerve axonal membranes, and its role in the practice of clinical neurophysiology has not been very well explored. This subthreshold superexcitability phenomenon of peripheral nerve axonal membranes was investigated using paired pulse stimuli at different interstimulus intervals (ISIs). Similar results have been shown to occur when applying these stimuli patterns to central nervous system axons in rabbits . Interestingly, the effect of superexcitability has a longer lasting effect on the axons of the central nervous system when compared to peripheral nerve fibers.

Bostock has shown that if the conditioning stimulus evokes a response, the stimulation intensity needed by the second stimulus to depolarize the axon again, producing a second response (test stimulus), decreases as much as 28%. Yet, even in the case where the first stimulus does not cause the membrane to depolarize, the stimulation intensity needed to generate an action potential from the second stimuli decreases to around 4%–9% . More research needs to be done focusing on these superexcitability phenomena to better understand its role in intraoperative neuromonitoring (ION), especially the effects of subthreshold short trains of stimuli on membrane excitability.

8.2

Methodology

Using the methodology of Bostock, with some modifications that will be described later, can better help us to understand the effects of train stimulation applied during intra-ION. With this in mind, we investigated the behavior of peripheral axons in response to a train of stimuli at threshold and subthreshold intensities in both healthy awake volunteers and anesthetized patients.

Instead of using paired pulses, we applied repetitive subthreshold trains with two to five stimuli at very short ISIs to both the median and facial nerves. This modified technique allowed us to investigate how the integrative action of the peripheral nerve axonal membrane may be utilized to convert a theoretically ineffective subthreshold train of stimuli into an effective train that can generate an action potential.

8.2.1

Test subjects

The average age of the awake group was 40 years (two females) and that of the surgical group was 44 years (seven females). Neither group had electrophysiological signs of carpal tunnel syndrome or facial neuropathy.

The median nerve was tested from the wrists of 6 healthy awake volunteers (12 hands) done in a relaxed environment and in 17 patients (29 hands) during surgeries for low thoracic or lumbar spine procedures already utilizing ION. The extracranial portion of the facial nerve was stimulated at the stylomastoid foramen in 10 patients (10 facial nerves) during surgeries for the correction of facial vascular malformations already utilizing ION ( Fig. 8.1 ).