What question did this study set out to answer?

To explore the effects of tonic electrocutaneous stimulation (ECS) on C-fiber-mediated pain perception in healthy individuals.

March 16, 2026Open Access

A tonic electrocutaneous stimulation paradigm for graded sensory C-fiber engagement in healthy subjects

YKYoungsun KongUniversity of Connecticut APAndrew PeitzschUniversity of Connecticut RMRiley McNaboeUniversity of Connecticut

Key Points

To explore the effects of tonic electrocutaneous stimulation (ECS) on C-fiber-mediated pain perception in healthy individuals.
Conducted a controlled experiment with 21 participants using varied levels of ECS for 60 seconds.
Delivered ECS parameters targeting C-fiber, Aδ-fiber, and Aβ-fiber activities.
Simultaneously recorded skin conductance response and visual analog scale pain ratings.
ECS at medium and high intensities led to significantly higher self-reported pain scores and sympathetic nervous system activation compared to lower intensity.
Very strong correlation observed between pain intensity and ECS levels (r ≥ 0.90, p < .001).
SCR and SCL showed moderate correlations during ECS, with SCL correlations decreasing significantly after 30 seconds.

Abstract

Introduction Long-term pain models provide valuable proxies for studying physiological changes associated with chronic pain, which is commonly associated with sustained C-fiber-mediated nociceptive input and central sensitization, and are particularly useful in therapeutic and drug development research. We investigated tonic electrocutaneous stimulation (ECS), a method that enables precise temporal control and adjustable intensity within safe limits, using a 5 Hz sine-wave waveform intended to bias sensory responses toward C-fibers-mediated activity. Methods Twenty-one participants underwent three levels of personalized, 60-second ECS delivered at parameters intended to bias sensory responses toward C-fiber-mediated activity, three levels of short-term ECS using parameters commonly associated with Aδ-fiber-mediated responses, and mild long-term ECS using parameters commonly associated with Aβ-fiber-mediated activity as a non-painful control, skin conductance response (SCR) and level (SCL), continuous self-reported visual analog scale (VAS) pain ratings were recorded simultaneously. Results The low-, medium-, and high-intensity ECS conditions produced statistically distinct self-reported pain scores and differentiable sympathetic nervous system (SNS) activation patterns in SCR and SCL. Compared to the non-painful control, low-intensity C-fiber-biased ECS did not differ in pain perception or SNS activity, whereas medium and high intensities elicited significantly greater responses. Repeated-measures correlation analysis revealed very strong associations between VAS scores and stimulus intensity across the entire stimulation period ( r ≥ 0.90, p .001). Both SCR and SCL exhibited fair correlation coefficients throughout stimulation ( r = 0.35-0.58, p .05), while SCL correlations declined to poor, non-significant levels after first 30 seconds ( r = -0.05-0.22, p = n.s. ). Conclusion Our proposed model provides a controllable and reproducible approach for inducing long-term, intensity-dependent pain in human subjects, offering a physiologically relevant experimental paradigm with high temporal precision.

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