Differential roles of mGluR1 and mGluR5 in brief and prolonged nociceptive processing in central amygdala neurons.

Abstract

The laterocapsular division of the central nucleus of the amygdala (CeA) is now defined as the "nociceptive amygdala" because of its high content of neurons that respond to painful stimuli. The majority of these neurons become sensitized in a model of arthritis pain. Here we address the role of G protein-coupled group I metabotropic glutamate receptor subtypes mGluR1 and mGluR5 in nociceptive processing under normal conditions and in pain-related sensitization. Extracellular single-unit recordings were made from 65 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimuli, background activity, receptive field size, and threshold were measured before and after induction of the kaolin/carrageenan mono-arthritis in one knee and before and during applications of agonists and antagonists into the CeA by microdialysis. All neurons received excitatory input from the knee(s) and responded most strongly to noxious stimuli. Before arthritis, a group I mGluR1 and mGluR5 agonist (DHPG, n = 10) potentiated the responses to innocuous and noxious stimuli. This effect was mimicked by an mGluR5 agonist (CHPG, n = 15). In the arthritis pain state (>6 h after induction), the facilitatory effects of DHPG (n = 9), but not CHPG (n = 7), increased. An mGluR1 antagonist (CPCCOEt) had no effect before arthritis (n = 12) but inhibited the responses of sensitized neurons in the arthritis pain state (n = 8). An mGluR5 antagonist (MPEP) inhibited brief nociceptive responses under normal conditions (n = 19) and prolonged nociception in arthritis (n = 8). These data suggest a change of mGluR1 function and activation in the amygdala in pain-related sensitization, whereas mGluR5 is involved in brief as well as prolonged nociception.

• Authors: Weidong Li, Volker Neugebauer
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 91 Issue 1 Pg. 13-24 (Jan 2004) ISSN: 0022-3077 [Print] United States
• PMID: 13679408 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 2-chloro-5-hydroxyphenylglycine
• 7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester
• Chromones
• Grm5 protein, rat
• Phenylacetates
• Pyridines
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor type 1
• Kaolin
• Methoxyhydroxyphenylglycol
• 6-methyl-2-(phenylethynyl)pyridine
• Glycine
• 3,4-dihydroxyphenylglycol

Topics

• Action Potentials (drug effects)
• Amygdala (cytology, physiology)
• Animals
• Arthritis (chemically induced, physiopathology)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Glycine (analogs & derivatives, pharmacology)
• Kaolin
• Male
• Methoxyhydroxyphenylglycol (analogs & derivatives, pharmacology)
• Neurons (classification, drug effects, physiology)
• Phenylacetates (pharmacology)
• Physical Stimulation
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate (agonists, antagonists & inhibitors, drug effects, physiology)