• Robin Jonas, Barbara Namer, Mark Schnakenberg, Sabrina Soares, Julius Pakalniskis, Richard Carr, Martin Schmelz, and Roman Rukwied.
• Department Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
• Eur J Pain. 2020 Jan 1; 24 (1): 122-133.

BackgroundSinusoidal current stimuli preferentially activate C-nociceptors. Sodium channel isoforms NaV1.7 and NaV1.8 have been implicated in this. Sympathetic efferent neurons lack NaV1.8 and were explored upon sinusoidal activation.MethodsQuantitative Sudomotor Axon Reflex Test (QSART) was performed in hairy (n = 16) and glabrous (n = 12) skin. Responses of sympathetic efferents (n = 10) and nociceptive afferents (n = 21) to sinusoidal current stimulation (4 Hz, 0.05-0.15 mA) were recorded in humans by microneurography (n = 11). Activation of sympathetic units upon supra-threshold sinusoidal currents (>0.8 mA) was recorded in pigs (n = 8).ResultsSinusoidal stimuli (4 Hz, 0.4 mA) evoked weak sweat output (30 ml/h/m2 ) in hairy skin compared to rectangular pulses (4 Hz, 5 mA, 53 ml/h/m2 , p < .00001, ANOVA). No change in sweat output was recorded from glabrous skin to sine wave stimuli. Sinusoidal current at intensities ranging from 0.05 to 0.15 mA activated almost all (85%) nociceptors but only 40% of sympathetic units in human. Stimuli lead to a significantly lower activation in sympathetic versus nociceptive fibres as measured by activity-dependent slowing (ADS) of conduction (sympathetic efferents average ADS 100 ± 0.2% vs. C-nociceptors average ADS 113 ± 4%, p < .003, ANOVA).ConclusionsSympathetic efferent neurons are less apt to convert slow depolarizations into action potentials as compared to nociceptors. Distinctive sodium channel expression patterns between nociceptors and sympathetic efferent neurons may account for this difference. Sinusoidal stimulation therefore provokes weak sweat responses and provides no alternative for clinical assessment of autonomic function.SignificanceC-nociceptors in hairy skin are activated by 4 Hz sinusoidal current stimulation at lower intensities than myelinated fibres. Sympathetic efferent neurons-albeit also unmyelinated-are less responsive to sinusoidal activation than nociceptors within the same skin area. Cutaneous sympathetic efferent neurons apparently are less apt than nociceptors to convert slow depolarization into action potentials.© 2019 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICR®.

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