Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala

Mol Pain. 2006 May 8;2:18. doi: 10.1186/1744-8069-2-18.

Abstract

Background: The latero-capsular part of the central nucleus of the amygdala (CeLC) is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs) and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1) receptors. Here we address the role of group II mGluRs.

Results: Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents from the pontine parabrachial (PB) area. A selective group II mGluR agonist (LY354740) decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM) than in control animals (IC50 = 15.0 nM). The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU) but not a GABAA receptor antagonist (bicuculline). LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate) were detected.

Conclusion: Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology
  • Amygdala / physiopathology*
  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / physiopathology
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds / therapeutic use
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Agonists / therapeutic use
  • Glutamates / pharmacology*
  • Male
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Pain / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Bridged Bicyclo Compounds
  • Excitatory Amino Acid Agonists
  • Glutamates
  • Receptors, Metabotropic Glutamate
  • alpha-ethylglutamic acid
  • eglumetad