Changes in Tetrodotoxin-Resistant C-Fibre Activity during Fatiguing Isometric Contractions in the Rat

Ivana Kalezic,Heinz Steffens

doi:10.1371/journal.pone.0073980

Ivana Kalezic, Heinz Steffens

Open Access

https://doi.org/10.1371/journal.pone.0073980

Copy DOI

Abstract

It is by now well established that tetrodotoxin-resistant (TTX-R) afferent fibres from muscle in the rat exhibit a multisensitive profile, including nociception. TTX-R afferent fibres play an important role in motor control, via spinal and supraspinal loops, but their activation and function during muscle exercise and fatigue are still unknown. Therefore, the specific effect of isometric fatiguing muscle contraction on the responsiveness of TTX-R C-fibres has been investigated in this study. To quantify the TTX-R afferent input we recorded the cord dorsum potential (CDP), which is the result of the electrical fields set up within the spinal cord by the depolarisation of the interneurons located in the dorsal horn, activated by an incoming volley of TTX-R muscle afferents. The changes in TTX-R CDP size before, during and after fatiguing electrical stimulation of the gastrocnemius-soleus (GS) muscle have been taken as a measure of TTX-R C-unit activation. At the end of the fatiguing protocol, following an exponential drop in force, TTX-R CDP area decreased in the majority of trials (9/14) to 0.75±0.03% (mean ± SEM) of the pre-fatigue value. Recovery to the control size of the TTX-R CDP was incomplete after 10 min. Furthermore, fatiguing trials could sensitise a fraction of the TTX-R C-fibres responding to muscle pinch. The results suggest a long-lasting activation of the TTX-R muscle afferents after fatiguing stimulation. The role of this behaviour in chronic muscle fatigue in connection with pain development is discussed. Accumulation of metabolites released into the interstitium during fatiguing stimulation might be one of the reasons underlying the C-fibres’ long-lasting activation.

Highlights

It is well established that muscle fatigue and related pain syndromes accompany powerful and long-lasting activation of high-threshold muscle afferents [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
The heterogeneous family of small-diameter afferent fibres embraces a particular fraction of fibres expressing a high density of tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSC) with a conduction velocity predominantly within the Cfibre range [19;20], see [21,22,23]
The projection zone of TTX-R gastrocnemius–soleus (GS) afferent fibres in the rat spinal cord has been described recently, the synaptic field potential of the TTX-R muscle afferents reached their maximum value in lamina IV-VI of the dorsal horn [24]

Summary

Introduction

It is well established that muscle fatigue and related pain syndromes accompany powerful and long-lasting activation of high-threshold muscle afferents [1,2,3,4,5,6,7,8,9,10,11,12,13,14] This activation evokes complex effects in the central nervous system (CNS). It provides the CNS with nociceptive information from the muscle It plays a substantial role in the development of adaptive segmental motor reactions, through rearrangement of complex spinal pre-motoneuronal network, recently mapped using c-Fos neuronal activity labelling in rats [9] and cats [15]. The question of the modality of TTX-R muscle afferents is still under discussion

Objectives

Methods

Results

Discussion

Conclusion