Microneurography as a tool to study the function of individual C-fiber afferents in humans: responses from nociceptors, thermoreceptors, and mechanoreceptors

Abstract

The technique of microneurography—recording neural traffic from nerves in awake humans—has provided us with unrivaled insights into afferent and efferent processes in the peripheral nervous system for over 50 years. We review the use of microneurography to study single C-fiber afferents and provide an overview of the knowledge gained, with views to future investigations. C-fibers have slowly conducting, thin-diameter, unmyelinated axons and make up the majority of the fibers in peripheral nerves (~80%). With the use of microneurography in humans, C-fiber afferents have been differentiated into discrete subclasses that encode specific qualities of stimuli on the skin, and their functional roles have been investigated. Afferent somatosensory information provided by C-fibers underpins various positive and negative affective sensations from the periphery, including mechanical, thermal, and chemical pain (C-nociceptors), temperature (C-thermoreceptors), and positive affective aspects of touch (C-tactile afferents). Insights from microneurographic investigations have revealed the complexity of the C-fiber system, methods for delineating fundamental C-fiber populations in a translational manner, how C-fiber firing can be used to identify nerve deficits in pathological states, and how the responses from C-fibers may be modified to change sensory percepts, including decreasing pain. Understanding these processes may lead to future medical interventions to diagnose and treat C-fiber dysfunction. NEW & NOTEWORTHY The technique of microneurography allows us to directly investigate the functional roles of single C-fiber afferents in awake human beings. Here we outline and discuss the current field of C-fiber research on this heterogeneous population of afferents in healthy subjects, in pathological states, and from a translational perspective. We cover C-fibers encoding touch, temperature, and pain and provide perspectives on the future of C-fiber microneurography investigations in humans.

Proprioceptors in Cephalic Muscles

“…Recent studies, using immunohistochemistry techniques associated with specific markers related to mechanization, have shown that facial muscles [34,41,42] and some pharyngeal muscles [43] have differentiated sensory structures that presumably replace proprioceptors. However, it cannot be ruled out that sensitive nerve fibers reaching the muscles (especially nociceptive ones) can function as mechanoreceptorsproprioceptors (see [44]).…”

Studying human nociceptors: from fundamentals to clinic

“… 219 It is thought they may mediate the burning sensation felt at extreme hot or cold temperatures. 197 Their maximum firing frequency to cold stimuli is lower than for mechanical and heat stimuli. 217 This suggests a unique mechanism for the encoding of noxious cold temperatures.…”

“…While C-fibre nociceptors are studied using microneurography, Aδ nociceptors remain difficult to study. 197 Only recently were a class of human nociceptors with Aβ conduction velocities identified. 17 Hence, we have a limited understanding of human A-fibre nociceptor physiology and their role in chronic pain states.…”

“… 215 These findings suggest that coding of mechanically evoked pain by C-mechanosensitive afferents is intensity dependent. 197 …”

Pain, Touch, and Decision Making : Behavioral and Brain Responses to Affective Somatosensory Stimulation

“…This increase in firing frequency correlated with an increase in pain intensity ratings to the same stimuli in humans, suggesting that C-fibers signal pain in response to heat stimuli. Microneurography studies in humans have also indicated their involvement in various kinds of pain (for a review, see Ackerley & Watkins, 2018). In contrast, patients with a hereditary condition that involves a severe reduction of C-fibers (and moderate reduction of Ad fibers) have reduced pain sensation (Einarsdottir et al, 2004;Minde et al, 2004).…”