mGluR1 and mGluR5 antagonists in the amygdala inhibit different components of audible and ultrasonic vocalizations in a model of arthritic pain

Pain has a strong emotional component. The amygdala plays a key role in emotionality and is also involved in pain processing and pain modulation. Our previous Studies showed an important role of group I metabotropic glutamate receptors (mGluRs) in pain-related synaptic plasticity and sensitization of neurons in the central nucleus of the amygdala (CeA). Here we address the roles of mGluR1 and mGluR5 subtypes in the CeA in the modulation of supraspinally organized behavioral responses in a model of arthritic pain. Audible and ultrasonic (25+/-4 kHz) vocalizations were measured in awake rats during and after innocuous and noxious stimulation ( 15 s) of the knee joint. Vocalizations were recorded in the same animals before arthritis, 6 h after arthritis induction and during administration of antagonists selective for mGIUR1 (CPCCOEt) and mGluR5 (MPEP) into the CeA through stereotaxically implanted microdialysis probes. The duration of audible and ultrasonic vocalizations increased in the arthritic pain state. The duration of vocalizations during stimulation (VDS), which are organized at the brainstem level. was significantly reduced by CPCCOEt but not by MPEP. Vocalizations that continued after stimulation (VAS). which are organized in the limbic forebrain, particularly the amygdala, were inhibited by CPCCOEt and MPEP. These findings suggest differential roles of mGluR1 and mGluR5 in the CeA in pain-related vocalizations. Both mGluR1 and mGluR5 contribute to vocalizations 2enerated in the ainygdala whereas niGluR1, but not mGIuR5, is involved in the amygdala-mediated modulation of vocalizations originating from activity in the brainstem. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.