Peripheral nerve maturation and excitability properties from early childhood: Comparison of motor and sensory nerves

Highlights

• Understanding maturation is essential to interpret paediatric nerve studies.

• Standardised pattern of axonal maturation is observed in motor and sensory axons.

• Biophysical differences occur in sensory axons from early childhood.

Abstract

Objective

Understanding of maturational properties of sensory and motor axons is of central importance for determining the impact of nerve changes in health and in disease in children and young adults.

Methods

This study investigated maturation of sensory axons using axonal excitability parameters of the median nerve in 47 children, adolescents and young adults (25 males, 22 females; age range 1–25 years) and compared them to concurrent motor studies.

Results

The overall pattern of sensory maturation was similar to motor maturation demonstrating prolongation of the strength duration time constant (P < 0.001), reduction of hyperpolarising threshold electrotonus (P = 0.002), prolongation of accommodation half-time (P = 0.005), reduction in hyperpolarising current-threshold slope (P = 0.03), and a shift to the right of the refractory cycle curve (P < 0.001), reflecting changes in passive membrane properties and fast potassium channel conductances. Sensory axons, however, had a greater increase in strength duration time constant and more attenuated changes in depolarising threshold electrotonus and current-threshold parameters, attributable to a more depolarised resting membrane potential evident from early childhood and maintained in adults. Peak amplitude was established early in sensory axons whereas motor amplitude increased with age (P < 0.001), reflecting non-axonal motor unit changes.

Conclusions

Maturational trajectories of sensory and motor axons were broadly parallel in children and young adults, but sensory-motor differences were initiated early in maturation.

Significance

Identifying the evolution of biophysical changes within and between sensory and motor axons through childhood and adolescence is fundamental to understanding developmental physiology and interpreting disease-related changes in immature nerves.

Introduction

Appropriate maturation of the sensory and motor components of the neuraxis is essential for physiological processes contributing to development. The normal development of sensory and motor skills through infancy, childhood and adolescence occurs sequentially and in a predictable sequence (Frankenburg and Dodds, 1967). In adults, peripheral sensory nerves are fundamentally different from motor nerves in their anatomical organisation (Preston and Shapiro, 2013) and biophysical properties (Bostock et al., 1994, Kiernan et al., 1996, Bostock and Rothwell, 1997, Howells et al., 2012), enabling optimal physiological function. In disease, however, these differences may explain the differential response of sensory and motor nerves to various stressors. Sensory and motor axons are differentially susceptible to disease processes, resulting in sensory predominant phenotypes such as chemotherapy induced peripheral neuropathy (Kandula et al., 2016), and motor phenotypes such motor neuron diseases (Priori et al., 2002).

The manifestation of neurological disease processes is also age-dependent and susceptibility to and progression of nervous system pathology is vastly different in children compared to adults (McMillan et al., 2013, Yilmaz et al., 2014). While this is multifactorial, delineating and comparing peripheral sensory and motor axonal maturation through childhood and adolescence is essential to fully understand clinical aspects of neurological disease in the paediatric age group. Efficiency of neural conduction is dependent on multiple factors including myelination, nerve diameter, inter-nodal distance and ion channel distribution which reach adult configurations at different ages (Gutrecht and Dyck, 1970, Wagner and Buchthal, 1972).

Specialised axonal excitability studies provide information regarding axonal biophysical properties in vivo, including active properties of the nerve such as ion channel and pump function as well as passive properties such as internodal length, diameter and myelination (Kiernan et al., 2000, Kiernan et al., 2001, Krishnan et al., 2009). Axonal excitability studies have been used to examine maturation of motor nerves and to understand motor axonal pathophysiology in paediatric neuropathies (Farrar et al., 2013, Farrar et al., 2017, Menezes et al., 2016), but the unique developmental properties of sensory nerves are yet to be elucidated. The aim of this study was to determine the physiological basis for changes in sensory nerves through childhood, adolescence and young adulthood using axonal excitability parameters and compare them to motor nerves, enabling a greater understanding of the impact of maturational changes in health and in disease. This study also provides sensory control data to enable comparison for paediatric axonal excitability studies.