Neural Signal Processing: The Underestimated Contribution of Peripheral Human C-Fibers

Abstract

The microneurography technique was used to analyze use-dependent frequency modulation of action potential (AP) trains in human nociceptive peripheral nerves. Fifty-one single C-afferent units (31 mechano-responsive, 20 mechano-insensitive) were recorded from cutaneous fascicles of the peroneal nerve in awake human subjects. Trains of two and four suprathreshold electrical stimuli at interstimulus intervals of 20 and 50 msec were applied to the receptive fields of single identified nociceptive units at varying repetition rates. The output frequency (interspike interval) recorded at knee level was compared with the input frequency (interstimulus interval) at different levels of accumulated neural accommodation. At low levels of use-dependent accommodation (measured as conduction velocity slowing of the first action potential in a train), intervals between spikes increased during conduction along the nerve. At increasing levels of neural accommodation, intervals decreased because of a relative supernormal period (SNP) and asymptotically approached the minimum "entrainment" interval of the nerve fiber (11 +/- 1.4 msec) corresponding to a maximum instantaneous discharge frequency (up to 190 Hz). For neural coding, this pattern of frequency decrease at low activity levels and frequency increase at high levels serves as a mechanism of peripheral contrast enhancement. The entrainment interval is a good minimum estimate for the duration of the refractory period of human C-fibers. At a given degree of neural accommodation, all afferent C-units exhibit a uniform pattern of aftereffects, independent of fiber class. The receptive class of a fiber only determines its susceptibility to accommodate. Thus, the time course of aftereffects and existence or absence of an SNP is fully explained by the amount of preexisting accommodation.

Perceptual Correlates of Nociceptive Long-Term Potentiation and Long-Term Depression in Humans

“…These protocols had been shown previously to induce LTP or LTD at primary afferent synapses with neurons of lamina II of the rat spinal cord (Randic et al, 1993;Liu and Sandkühler, 1997;Sandkühler et al, 1997;Svendsen et al, 1998). HFS corresponds to the burst mode of nociceptive afferents, which even in C fibers may reach discharge rates of up to 200 Hz for short periods of time (Weidner et al, 2002). LFS corresponds to the low-frequency discharge that nociceptive afferents can maintain for longer periods of time.…”

Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans

“…High frequency CES mimics a burst mode of nociceptive input, e.g., discharge at these high rates at the beginning of a noxious mechanical stimulus or injury (Handwerker et al, 1987). C-fibers may also instantaneously discharge at rates up to 200 Hz in humans (Weidner et al, 2002). However, in normal conditions C-fibers do not fire except for a few spikes at the high frequencies required in experimentally induced LTP-like pain amplification (Ji et al, 2003).…”

Activity-Dependent Modulation of Axonal Excitability in Unmyelinated Peripheral Rat Nerve Fibers by the 5-HT(3) Serotonin Receptor

“…In recent studies, the sequence of changes of axonal excitability after an action potential (i.e., the recovery cycle) have been analyzed in much detail (Bostock et al 2003;Gee et al 1996;Shin and Raymond 1991;Weidner et al 2000Weidner et al , 2002. The recovery cycle can last for several hundred milliseconds and consists of periods with enhanced and reduced axonal excitability.…”