Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo

Robert H. Goldstein, Omer Barkai, Almudena Íñigo-Portugués, Ben Katz, Shaya Lev, Alexander M. Binshtok*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Nociceptive terminals possess the elements for detecting, transmitting, and modulating noxious signals, thus being pivotal for pain sensation. Despite this, a functional description of the transduction process by the terminals, in physiological conditions, has not been fully achieved. Here, we studied how nociceptive terminals in vivo convert noxious stimuli into propagating signals. By monitoring noxious-stimulus-induced Ca2+ dynamics from mouse corneal terminals, we found that initiation of Na+ channel (Nav)-dependent propagating signals takes place away from the terminal and that the starting point for Nav-mediated propagation depends on Nav functional availability. Acute treatment with the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) resulted in a shift of the location of Nav involvement toward the terminal, thus increasing nociceptive excitability. Moreover, a shift of Nav involvement toward the terminal occurs in corneal hyperalgesia resulting from acute photokeratitis. This dynamic change in the location of Nav-mediated propagation initiation could underlie pathological pain hypersensitivity. Goldstein et al. describe the location of the sodium spike initiation zone (Nav-SIZ) in nociceptive peripheral terminals in vivo and show that this location is dynamic.

Original languageAmerican English
Pages (from-to)801-812.e5
JournalNeuron
Volume102
Issue number4
DOIs
StatePublished - 22 May 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • SIZ
  • SIZ plasticity
  • cornea
  • hyperalgesia
  • inflammation
  • nociceptor
  • nociceptor terminal
  • proinflammatory cytokines
  • slow inactivation
  • sodium channels

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