The Population Response of A- and C-Fiber Nociceptors in Monkey Encodes High-Intensity Mechanical Stimuli

Abstract

The peripheral neural mechanism of pain to mechanical stimuli remains elusive. C-fiber nociceptors do not appear to play a major role in mechanical pain sensation, because the stimulus-response function of mechanically sensitive C-fiber nociceptors to punctate mechanical stimuli applied to the most sensitive region in the receptive field (the hot spot) reaches a plateau at force levels insufficient to produce pain in humans. However, studies at the hot spot give an incomplete understanding of the inputs of nociceptors to the spinal cord. To estimate how the population of nociceptors responds to a punctate stimulus, it is necessary to know how the response varies with the position within the receptive field. For A-fiber and C-fiber nociceptors, we systemically measured the response to a 100 m wide blade stimulus as a function of position in the receptive field at different force levels. Highly reproducible receptive field response maps that contained multiple peaks and valleys were obtained. Some peaks were only 100 m wide. As force increased, the response and width of the peaks increased, the response in valleys increased, and new peaks appeared. The averaged response across the map provides an estimate of the population response and was found to increase monotonically with force over a large stimulus range for both A-fiber and C-fiber nociceptors. These data provide evidence that both C-fiber and A-fiber nociceptors may encode high-intensity mechanical stimuli.

Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach

“…It can be seen that the FI curve of the Aδ-Neuroid matched the experimental curve (Figure 2c), whereas the FI curve of the HTC-Neuroid increased monotonically (Figure 2f) instead of reaching a plateau as reported previously by Slugg et al (2000). However, in a subsequent study (Slugg et al, 2004), it was demonstrated that the average response of C-fiber nociceptors across the receptive field does not reach a plateau, but increases monotonically with mechanical stimulus intensity. This suggests that the Neuroid might be used to predict the "average" response of a specific subpopulation of nociceptive primary afferents as long as the variability of experimental data is taken into account.…”

“…Discrepancies may be attributed to differences in the experimental protocol used to quantify the response properties of primary afferent and dorsal horn neurons (current injection vs. peripheral stimuli; in vivo vs. in vitro). While Neuroids representing primary afferent neurons were configured according to the response of these cells to peripheral mechanical stimuli (Cain et al, 2001;Slugg et al, 2000Slugg et al, , 2004, Neuroids representing dorsal horn neurons were configured according to the response of these cells to current injections (Ruscheweyh and Sandkühler, 2002), since no recent studies seem to be available to extract relevant features of the dorsal horn neurons responses to peripheral mechanical stimuli (e.g. the frequencyintensity curve).…”

High-frequency electrical stimulation of the human skin induces heterotopical mechanical hyperalgesia, heat hyperalgesia, and enhanced responses to nonnociceptive vibrotactile input

“…In primates, it has been shown that high-intensity mechanical punctate stimuli (e.g., von Frey probes) are capable of activating A␦-and C-fiber nociceptors (Slugg et al 2004). However, in healthy humans, von Frey stimulation usually does not cause pain.…”

The implementation of the Neuroid in the Gate Control System leads to new ideas about pain processing

“…In fact, the flatness observed in C-fiber responses suggested that they could not encode high intensity mechanical stimuli. Subsequent studies show that the average response of C-fiber nociceptors across the receptive field does not reach a plateau, but increases monotonically with stimulus intensity (Slugg et al, 2004). This leads to the assumption that individual and collective responses of Aβ-fibres may also differ.…”