Differential Changes of Group II and Group III mGluR Function in Central Amygdala Neurons in a Model of Arthritic Pain

Abstract

Metabotropic glutamate receptors (mGluRs) play important roles in neuroplasticity and disorders such as persistent pain. Group I mGluRs contribute to pain-related sensitization and synaptic plasticity of neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC), although the roles of groups II and III mGluRs are not known. Extracellular single-unit recordings were made from 60 CeLC neurons in anesthetized adult rats. Background activity and evoked responses were measured before and during the development of the kaolin/carrageenan-induced knee-joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. A selective group III mGluR agonist (LAP4) inhibited CeLC neurons' responses to stimulation of the knee and ankle in arthritis (n = 7) more potently than under normal conditions (n = 14). A selective group II agonist (LY354740) inhibited responses under normal conditions (n = 12) and became more potent in inhibiting responses to noxious stimulation of the knee in arthritis (n = 10). The effect of LY354740 on innocuous stimulation of the knee and stimulation of the ankle did not change in arthritis. Antagonists for groups II (EGLU, n = 9) and III (UBP1112, n = 8) had no effects under normal conditions. In arthritis, UPB1112 (n = 5) facilitated the responses to stimulation of knee and ankle, whereas EGLU (n = 5) selectively increased the responses to stimulation of the knee. These data suggest that mGluRs of groups II and III can inhibit nociceptive processing in CeLC neurons. The increased function and endogenous activation of group II mGluRs in the arthritis pain model appear more input-selective than the general changes of group III mGluRs.