Long-term actions of interleukin-1β on K+, Na+ and Ca2+ channel currents in small, IB4-positive dorsal root ganglion neurons; possible relevance to the etiology of neuropathic pain

J Neuroimmunol. 2019 Jul 15:332:198-211. doi: 10.1016/j.jneuroim.2019.05.002. Epub 2019 May 4.

Abstract

Excitation of dorsal root ganglion (DRG) neurons by interleukin 1β (IL-1β) is implicated in the onset of neuropathic pain. To understand its mechanism of action, isolectin B4 positive (IB4+) DRG neurons were exposed to 100pM IL-1β for 5-6d. A reversible increase in action potential (AP) amplitude reflected increased TTX-sensitive sodium current (TTX-S INa). An irreversible increase in AP duration reflected decreased Ca2+- sensitive K+ conductance (BK(Ca) channels). Different processes thus underlie regulation of the two channel types. Since changes in AP shape facilitated Ca2+ influx, this explains how IL-1β facilitates synaptic transmission in the dorsal horn; thereby provoking pain.

Keywords: BK(Ca) channel; Electrophysiology; Ion channel; K(+) channel; Na(+) channel; Nerve injury; Neuroinflammation; Nociceptor; Peripheral neuropathy; Primary afferent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cell Size
  • Ganglia, Spinal / cytology*
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Interleukin-1beta / pharmacology*
  • Ion Channel Gating / drug effects*
  • Male
  • Nerve Growth Factor / pharmacology
  • Neuralgia / etiology*
  • Neuralgia / metabolism
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Plant Lectins / analysis
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / ultrastructure
  • Sodium Channels / drug effects*
  • Sodium Channels / metabolism

Substances

  • Calcium Channels
  • Glial Cell Line-Derived Neurotrophic Factor
  • Griffonia simplicifolia lectins
  • Interleukin-1beta
  • Peptides
  • Plant Lectins
  • Potassium Channels
  • Sodium Channels
  • tetrodotoxin-binding protein
  • iberiotoxin
  • Nerve Growth Factor

Grants and funding