Analysis of Nociceptive Information Encoded in the Temporal Discharge Patterns of Cutaneous C-Fibers

Abstract

The generation of pain signals from primary afferent neurons is explained by a labeled-line code. However, this notion cannot apply in a simple way to cutaneous C-fibers, which carry signals from a variety of receptors that respond to various stimuli including agonist chemicals. To represent the discharge patterns of C-fibers according to different agonist chemicals, we have developed a quantitative approach using three consecutive spikes. By using this method, the generation of pain in response to chemical stimuli is shown to be dependent on the temporal aspect of the spike trains. Furthermore, under pathological conditions, gamma-aminobutyric acid resulted in pain behavior without change of spike number but with an altered discharge pattern. Our results suggest that information about the agonist chemicals may be encoded in specific temporal patterns of signals in C-fibers, and nociceptive sensation may be influenced by the extent of temporal summation originating from the temporal patterns.

Maximum axonal following frequency separates classes of cutaneous unmyelinated nociceptors in the pig

“…However, is important to note that pain intensity is not simply encoded by frequency, and that spike timing and temporal pattern are also of crucial importance (Cho et al . 2016; Barkai et al . 2020).…”

Hyperpolarization‐activated channels shape temporal patterns of ectopic spontaneous discharge in C‐nociceptors after peripheral nerve injury

“…A redistribution of HCN channels after nerve damage would have a decisive influence on these spike trains. It has long been suggested that both the magnitude and the quality of pain sensation are encoded by the temporal summation of the nociceptive discharge (Koltzenburg and Handwerker, ; Cho et al., ) and that different responses before and after a nerve injury might be associated with the temporal patterns of spontaneous spikes (Sandkühler, ). However, the relevance of the temporal patterns of ectopic discharges in the nociceptive message has never been examined in depth before.…”

The Input-Output Relation of Primary Nociceptive Neurons is Determined by the Morphology of the Peripheral Nociceptive Terminals

“…This change in peak instantaneous frequency may be too narrow to encode and convey the changes in response to stimuli. We, therefore, hypothesized that in addition to the spike rate coding (Adrian and Zotterman, 1926), the nociceptive neurons might also use "temporal" coding to integrate and encode the information about different response properties via different timing patterns of spikes (Cho et al, 2016). Accordingly, we analyzed the spiking activity over time following a capsaicin-current stimulation of all terminals in the "realistic" terminal tree in normal conditions, in inflammatory hyperalgesia conditions, in which the SIZ was shifted toward the terminals and in neuropathic pain conditions, in which sub-and suprathreshold current noise was injected (Figure 11D).…”

“…We show that in modeled pathological conditions in which nociceptive neurons become hyperexcitable, the changes in their gain are encoded by the differences in the spike arrival time. The differences in spike patterns between capsaicin and GABA-evoked responses were recently correlated with the differences in the resulting pain sensation following either capsaicin or GABA stimulation (Cho et al, 2016). Thus, the difference in the timing pattern of spikes could convey important information regarding the gain of the inputoutput properties of the nociceptive neurons.…”