Highlights:
- •Human skin C-nociceptors have an unexpectedly long chronaxie (about 15 ms)
- •Half-sine stimuli adapted to long chronaxie facilitate electrical stimulation of skin nociceptors
- •Currents for excitation of polymodal C-nociceptors in pig paralleled pain ratings in humans
Abstract
Classically, to electrically excite C-nociceptors, rectangular pulses are used with
a duration close to the estimated chronaxie of C-fibres (about 2 ms). Recent results
using slow depolarizing stimuli suggest longer chronaxies. We therefore set out to
optimize C-fiber stimulation based on recordings of single C-nociceptors in-vivo and C-fiber compound-action-potentials (C-CAP) ex-vivo using half-sine shaped stimuli of durations between 1 and 250ms. Single fiber (n=45) recording in pigs revealed high chronaxie values for C-touch fibers (15.8 ms), polymodal-
(14.2 ms) and silent-nociceptors (16.8 ms). Activation thresholds decreased 2-3fold
in all fiber classes when increasing the duration of half-sine pulses from 1 to 25
ms (p<0.05). C-CAPs strength-duration curves of the pig saphenous nerve (n=7) showed
the highest sensitivity for half-sine durations between 10 and 25 ms. Half-maximum
currents for C-CAPS were reduced 3fold compared to rectangular pulses (p<0.01) whereas
the opposite was found for A-fiber compound action potentials. Psychophysics in humans
(n=23) revealed that half-sine stimulus durations >10 ms reduced detection thresholds,
pain thresholds and stimulus current amplitudes required to generate a pain rating
of 3 on an 11-point Numeric Rating Scale (NRS) as compared to 1 ms rectangular pulses
(p<0.05). Increasing the duration from 1 to 25 ms led to a 4fold amplitude reduction
for pain-thresholds and stimuli caused an axon-reflex flare. Excitability of single
polymodal nociceptors in animals paralleled human psychophysics and we conclude optimized
half-sine pulses facilitate C-nociceptor activation.
Perspective
Electrical stimulation with longer lasting half-sine wave pulses preferentially activates
C-nociceptors and changes in the strength duration curve may identify nociceptor hyperexcitability
in patients with neuropathic pain.
Keywords
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Article info
Publication history
Accepted:
January 10,
2023
Received in revised form:
December 21,
2022
Received:
September 27,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.
