Effects of sciatic nerve axotomy on excitatory synaptic transmission in rat substantia gelatinosa

J Neurophysiol. 2009 Dec;102(6):3203-15. doi: 10.1152/jn.00296.2009. Epub 2009 Sep 30.

Abstract

Injury or section of a peripheral nerve can promote chronic neuropathic pain. This is initiated by the appearance and persistence of ectopic spontaneous activity in primary afferent neurons that promotes a secondary, enduring increase in excitability of sensory circuits in the spinal dorsal horn ("central sensitization"). We have previously shown that 10-20 days of chronic constriction injury (CCI) of rat sciatic nerve produce a characteristic "electrophysiological signature" or pattern of changes in synaptic excitation of five different electrophysiologically defined neuronal phenotypes in the substantia gelatinosa of the dorsal horn. Although axotomy and CCI send different signals to the dorsal horn, we now find, using whole cell recording, that the "electrophysiological signature" produced 12-22 days after sciatic axotomy is quite similar to that seen with CCI. Axotomy thus has little effect on resting membrane potential, rheobase, current-voltage characteristics, or excitability of most neuron types; however, it does decrease excitatory synaptic drive to tonic firing neurons, while increasing that to delay firing neurons. Since many tonic neurons are GABAergic, whereas delay neurons do not contain gamma-aminobutyric acid, axotomy may reduce synaptic excitation of inhibitory neurons while increasing that of excitatory neurons. Further analysis of spontaneous and miniature (tetrodotoxin-resistant) excitatory postsynaptic currents is consistent with the possibility that decreased excitation of tonic neurons reflects loss of presynaptic contacts. By contrast, increased excitation of "delay" neurons may reflect increased frequency of discharge of presynaptic action potentials. This would explain how synaptic excitation of tonic cells decreases despite the fact that axotomy increases spontaneous activity in primary afferent neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Axotomy / methods*
  • Biophysics
  • Calcium-Binding Proteins / metabolism
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • GABA Antagonists / pharmacology
  • Inhibitory Postsynaptic Potentials / drug effects
  • Laminectomy / methods
  • Microfilament Proteins
  • Patch-Clamp Techniques / methods
  • Pyridazines / pharmacology
  • Rats
  • Sciatic Nerve / physiology*
  • Substantia Gelatinosa / physiology*
  • Synapses / drug effects
  • Synapses / physiology*

Substances

  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Microfilament Proteins
  • Pyridazines
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • gabazine