Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice

Hoffmann T, Kistner K, Carr RW, Nassar MA, Reeh P, Weidner C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 158

Pages Range: 58-67

Journal Issue: 1

DOI: 10.1097/j.pain.0000000000000723

Abstract

The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 has previously been associated with inflammatory hyperalgesia. Na1.9 knockout (KO) mice, however, did not seem insensitive in conventional tests of acute nociception. Using electrophysiological, neurochemical, and behavioral techniques, we now show NaV1.9-null mice exhibit impaired mechanical and thermal sensory capacities and reduced electrical excitability of nociceptors. In single-fiber recordings from isolated skin, the electrical threshold of NaV1.9 KO C fibers was elevated by 55% and the median von Frey threshold was 32 mN in contrast to 8 mN in wild types (WTs). The prevalence of C mechano-heat-sensitive (CMH) fibers was only 25.6% in NaV1.9 KO animals compared to 75.8% in the WT group, and the heat threshold of these CMH fibers was 40.4°C in the control vs 44°C in the KO group. Compound action potential recordings from isolated sciatic nerve segments of NaV1.9 KO mice revealed lower activity-induced slowing of conduction velocity upon noxious heat stimulation: 8% vs 30% in WTs. Heat-induced calcitonin gene-related peptide release from the skin was less in the KO than in the WT group. The reduced noxious heat sensitivity was finally confirmed with the Hargreaves test using 2 rates of radiant heating of the plantar hind paws. In conclusion, NaV1.9 presumably contributes to acute thermal and mechanical nociception in mice, most likely through increasing the excitability but probably also by amplifying receptor potentials irrespective of the stimulus modality.

Authors with CRIS profile

Involved external institutions

Ruprecht-Karls-Universität Heidelberg Germany (DE) University of Sheffield United Kingdom (GB)

How to cite

APA:

Hoffmann, T., Kistner, K., Carr, R.W., Nassar, M.A., Reeh, P., & Weidner, C. (2017). Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice. Pain, 158(1), 58-67. https://doi.org/10.1097/j.pain.0000000000000723

MLA:

Hoffmann, Tal, et al. "Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice." Pain 158.1 (2017): 58-67.

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