Evoked bursting in injured Aβ dorsal root ganglion neurons: a mechanism underlying tactile allodynia

Pain. 2012 Mar;153(3):657-665. doi: 10.1016/j.pain.2011.11.030. Epub 2012 Jan 9.

Abstract

Chronic compression of rat dorsal root ganglion (CCD) produced tactile allodynia accompanied with hyperexcitability of the myelinated Aβ dorsal root ganglion (DRG) neurons. The Aβ DRG neuron hyperexcitability exhibits as bursting discharges in response to peripherally evoked action potentials (evoked bursting [EB]). The incidence of EB was significantly increased after chronic compression of DRG (CCD) (43.3%) vs control (13.3%). EB was maintained by oscillation of the membrane potential, and its duration was increased when the membrane potential was depolarized. EB was found to coexist in some neurons with spontaneous bursting (SB), but EB always occurred at a more negative membrane potential than SB. Afterdischarges of the wide dynamic range neurons of the dorsal horn in the spinal cord in response to electrical stimulation of Aβ afferent nerve fibers were suppressed by blocking EB of the DRG neurons. CCD neurons with EB exhibited increased current density of persistent sodium current (I(Nap)) and hyperpolarization-activated cation current (I(h)) and decreased α-dendrotoxin (α-DTX) sensitive current (I(DTX)). The increased I(h) activated by afterhyperpolarization of peripheral afferent action potential was necessary for EB generation and a balance between I(DTX) and I(Nap) might be necessary for EB maintenance. This study may suggest a role of EB of myelinated DRG neurons in development of allodynia after nerve injury and a potential pharmaceutical therapy in treating neuropathic allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / physiology*
  • Biophysics
  • Cardiovascular Agents / pharmacology
  • Chi-Square Distribution
  • Disease Models, Animal
  • Double-Blind Method
  • Elapid Venoms / pharmacology
  • Electric Stimulation
  • Female
  • Fourier Analysis
  • Ganglia, Spinal / pathology*
  • Hyperalgesia / physiopathology*
  • Male
  • Patch-Clamp Techniques
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / physiology*
  • Sodium Channel Blockers / pharmacology
  • Spinal Cord Compression / pathology*
  • Tetrodotoxin / pharmacology
  • Time Factors

Substances

  • Cardiovascular Agents
  • Elapid Venoms
  • Pyrimidines
  • Sodium Channel Blockers
  • ICI D2788
  • Tetrodotoxin
  • dendrotoxin