Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons

PLoS One. 2011 Apr 25;6(4):e18681. doi: 10.1371/journal.pone.0018681.


In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP)). The I(NaP) is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP) in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP), also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP) was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP) without affecting the transient sodium current (I(NaT)). Taken together, these results demonstrate for the first time that the I(NaP) blocker riluzole selectively inhibits I(NaP) and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP) of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / pathology*
  • Ganglia, Spinal / physiopathology
  • Hyperalgesia / complications
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology
  • Ion Channel Gating / drug effects*
  • Membrane Potentials / drug effects
  • Nerve Fibers / drug effects
  • Nerve Fibers / pathology
  • Neurons / drug effects
  • Neurons / pathology*
  • Radiculopathy / complications
  • Radiculopathy / pathology
  • Radiculopathy / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Riluzole / pharmacology*
  • Sodium Channel Blockers / pharmacology*
  • Sodium Channels / metabolism*


  • Sodium Channel Blockers
  • Sodium Channels
  • Riluzole