Slow depolarizing stimuli differentially activate mechanosensitive and silent C nociceptors in human and pig skin

Rukwied R, Thomas C, Obreja O, Werland F, Kleggetveit IP, Jorum E, Carr RW, Namer B, Schmelz M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Pain Lippincott, Williams & Wilkins

Book Volume: 161

Pages Range: 2119-2128

Journal Issue: 9

DOI: 10.1097/j.pain.0000000000001912

Abstract

High-threshold mechanosensitive and mechanoinsensitive ("silent") nociceptors have similar electrical thresholds for transcutaneous sine wave stimulation at 4 Hz that selectively activates cutaneous C nociceptors in human skin. Their fundamentally different functions particularly in chronic pain warrant differential stimulation protocols. We used transcutaneously delivered slow depolarizing stimuli (half-sine, 500 ms duration, 0.01-1 mA) in humans to assess intensity-response relations for the induction of pain psychophysically and recorded activation of mechanosensitive and silent nociceptors in healthy volunteers by microneurography. Differential C-fiber activation was confirmed in single-fiber recordings in pig allowing for stimulation amplitudes up to 10 mA. Perception and pain thresholds to half-sine wave pulses were 0.06 +/- 0.03 mA and 0.18 +/- 0.1 mA, respectively, and caused pain in an amplitude-dependent manner (n = 24). When matched for pain intensity, only sine wave stimulation induced an instant widespread axon reflex erythema (n = 10). In human microneurography, half-sine stimulation activated mechanosensitive nociceptors (n = 13), but only one of 11 silent nociceptors. In pig skin, the amplitude-dependent activation of mechanosensitive nociceptors was confirmed (0.2-1 mA, n = 28), and activation thresholds for most silent nociceptors (n = 13) were found above 10 mA. Non-nociceptive low-threshold mechanosensitive C fibers (n = 14) displayed lower activation thresholds for half-sine wave stimuli with an amplitude-dependent discharge increase between 0.01 and 0.1 mA. We conclude that transcutaneous electrical stimulation with 500-ms half-sine wave pulses between 0.2 and 1 mA causes amplitude-dependent pain by preferential activation of mechanosensitive C nociceptors.

Authors with CRIS profile

Barbara Namer Medizinische Fakultät

Additional Organisation(s)

Institut für Physiologie und Pathophysiologie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) University of Oslo NO Norway (NO) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO)

How to cite

APA:

Rukwied, R., Thomas, C., Obreja, O., Werland, F., Kleggetveit, I.-P., Jorum, E.,... Schmelz, M. (2020). Slow depolarizing stimuli differentially activate mechanosensitive and silent C nociceptors in human and pig skin. Pain, 161(9), 2119-2128. https://doi.org/10.1097/j.pain.0000000000001912

MLA:

Rukwied, Roman, et al. "Slow depolarizing stimuli differentially activate mechanosensitive and silent C nociceptors in human and pig skin." Pain 161.9 (2020): 2119-2128.

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