737: Bursts in mechanosensitive C-fibers probably propagate non-histaminergic itch sensation

Topic: Basic Science
Subtopic: Itch, Electrophysiology

Background and Aims: Itch and pain are distinct sensations that arise from the central integration of peripheral nerve signals. Both itch- and pain-inducing chemicals activate the same population of peripheral neurons—mechanosensitive C-fibers (CM)—which also respond to noxious heat(1). How these fibers differentially encode itch versus pain remains unclear.
We proposed that CM fibers may distinguish between itch and pain through differences in temporal patterns of action potential discharge (2). In particular, non-histaminergic pruritogens evoke a slow bursting firing pattern in approx. 35% of human CM´s, a pattern that has not been observed with algogens.
This specific firing pattern has not yet been systematically investigated and characterized in detail. Here, we present analyses of chemically evoked temporal discharge patterns in human peripheral nerve fibers, providing further evidence for a role of patterned activity in the encoding of itch(2).

Methods: Our study uses microneurography to record action potentials from single afferent CM-fibers in seven human volunteers induced by intracutaneous microinjection (30 µl) of various chemical substances (BAM8-22, beta alanine, and ET 1). In the present work, we analyzed the bursting activity of CM-fibers.
The signals were recorded by custom-made software DAPSYS and Spike2 in parallel. The data was analyzed using the traditional marking method and spike sorting algorithms of spike 2 software. The marking method identified fibers showing a "bursting" discharge pattern as well as single Spike detection via Spike 2.

Results: In CM fibers, all tested pruritogens induced either a “slow bursting” or a “non-bursting” temporal discharge pattern. In the present study, we provide, for the first time, detailed analyses of temporal discharge patterns in human CM fibers evoked by non-histaminergic pruritogens. We analyzed in 7 human participants CM-fiber activity caused by β-alanine, ET-1, and BAM 8-22. The slow bursting pattern varied across the C-fiber responses:
The overall firing rate ranged from approximately 0.2 to 1.2 Hz, with the highest rates observed during β-alanine responses, likely reflecting its longer-lasting activation of the fibers.
The inter-burst interval was ~20–100 s, with 3–6 bursts per response.
The proportion of spikes within bursts was highest for BAM8-22 (up to 80%) and lower for β-alanine and ET-1 (~40%).
Burst duration was 5–9 s, longest for β-alanine.
Within-burst ISI was 0.15–0.25 s, highest for BAM8-22.

Conclusions: These findings demonstrate that CM fibers responding to non-histaminergic pruritogens exhibit distinct temporal discharge patterns. Further studies are needed to investigate how such temporal coding relates to the perceived sensations of itch, as well as how these patterns may be altered in patients suffering from chronic itch and pain conditions.

References: 1. Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M. Separate Peripheral Pathways for Pruritus in Man. J Neurophysiol. Oktober 2008;100(4):2062–9.
2. Fiebig A, Leibl V, Oostendorf D, Lukaschek S, Frömbgen J, Masoudi M, u. a. Peripheral signaling pathways contributing to non-histaminergic itch in humans. J Transl Med. 12. Dezember 2023;21(1):908.

Presenting Author: Andrea Fiebig
Submitting Author: Andrea Fiebig

Senior Author: Barbara Namer

IASP 2026 Global Year theme of Neuropathic Pain: No

• Barbara Namer - Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine Julius-Maximilians University Würzburg, Würzburg, Germany
• David Berling - Research Center for Computational Biomedicine, Uniklinik RWTH Aachen, Aachen, Germany
• Ekaterina Kutafina - Institute for Biomedical Informatics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
• Alina Troglio - Institute for Biomedical Informatics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
• Jenny Tigerholm - Research Center for Computational Biomedicine, Uniklinik RWTH Aachen, Aachen, Germany
• Anna Maxion - Research Center for Computational Biomedicine, Uniklinik RWTH Aachen, Aachen, Germany