Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice. Issue 1 (15th September 2016)

• Record Type: Journal Article
• Authors: Hoffmann, Tal; Kistner, Katrin; Carr, Richard W.; Nassar, Mohammed A.; Reeh, Peter W.; Weidner, Christian
• Is Part Of: Pain. Volume 158:Issue 1(2017)
• Page Start: 58
• Page End: 67
• Publication Date: 2016-09-15
• Subjects: Voltage-gated sodium channels -- Unmyelinated fibers -- CGRP release -- Compound action potential -- Plantar test -- von Frey; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000723
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Nav 1.9 is important for thermal and mechanical sensitivity, most likely by acting as an amplifier for the transformation of generator currents into action potentials. Abstract: The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV 1.9 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 NaV 1.9-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 NaV 1.9 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 NaV 1.9 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 NaV 1.9 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, NaV 1.9 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.