Complementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signalling

Kühn H, Kappes L, Wolf K, Gebhardt L, Neurath M, Reeh P, Fischer MJ, Kremer A (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 10

Article Number: 2326

Journal Issue: 1

DOI: 10.1038/s41598-020-59092-2

Abstract

Acute pruritus occurs in various disorders. Despite severe repercussions on quality of life treatment options remain limited. Voltage-gated sodium channels (NaV) are indispensable for transformation and propagation of sensory signals implicating them as drug targets. Here, NaV1.7, 1.8 and 1.9 were compared for their contribution to itch by analysing NaV-specific knockout mice. Acute pruritus was induced by a comprehensive panel of pruritogens (C48/80, endothelin, 5-HT, chloroquine, histamine, lysophosphatidic acid, trypsin, SLIGRL, β-alanine, BAM8-22), and scratching was assessed using a magnet-based recording technology. We report an unexpected stimulus-dependent diversity in NaV channel-mediated itch signalling. NaV1.7−/− showed substantial scratch reduction mainly towards strong pruritogens. NaV1.8−/− impaired histamine and 5-HT-induced scratching while NaV1.9 was involved in itch signalling towards 5-HT, C48/80 and SLIGRL. Furthermore, similar microfluorimetric calcium responses of sensory neurons and expression of itch-related TRP channels suggest no change in sensory transduction but in action potential transformation and conduction. The cumulative sum of scratching over all pruritogens confirmed a leading role of NaV1.7 and indicated an overall contribution of NaV1.9. Beside the proposed general role of NaV1.7 and 1.9 in itch signalling, scrutiny of time courses suggested NaV1.8 to sustain prolonged itching. Therefore, NaV1.7 and 1.9 may represent targets in pruritus therapy.

Authors with CRIS profile

Helen Kühn Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Leonie Kappes Institut für Physiologie und Pathophysiologie Katharina Wolf Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lisa Gebhardt Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Peter Reeh Professur für Physiologie Andreas Kremer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Medizinische Universität Wien AT Austria (AT)

How to cite

APA:

Kühn, H., Kappes, L., Wolf, K., Gebhardt, L., Neurath, M., Reeh, P.,... Kremer, A. (2020). Complementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signalling. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-59092-2

MLA:

Kühn, Helen, et al. "Complementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signalling." Scientific Reports 10.1 (2020).

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