Block of NMDA and non-NMDA receptor activation results in reduced background and evoked activity of central amygdala neurons in a model of arthritic pain.

The latero-capsular division of the central nucleus of the amygdala (CeA) is now defined as the 'nociceptive amygdala' because of its high content of neurons activated exclusively or preferentially by noxious stimuli. Multireceptive (MR) neurons that respond to innocuous and, more strongly, to noxious stimuli become sensitized in arthritis pain. This form of nociceptive plasticity involves presynaptic group I metabotropic glutamate receptors, which increase glutamate release. Here we address the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Extracellular single-unit recordings were made from 25 CeA neurons in anesthetized rats. The neurons' responses to graded brief (15 s) mechanical stimuli, background activity, receptive field size and threshold were measured before and after the induction of kaolin/carrageenan arthritis in one knee and before and during drug applications into the CeA by microdialysis. All neurons examined received excitatory input from the knee(s) and were MR neurons. A selective NMDA receptor antagonist (AP5) inhibited responses to noxious stimuli more potently in the arthritic pain state (n = 6) than under control conditions before arthritis (n = 8) AP5 also inhibited the enhanced background activity and increased responses to normally innocuous stimuli in arthritis, but had no significant effects on these parameters under control conditions. A selective non-NMDA receptor antagonist (NBQX) inhibited background activity and evoked responses under normal control conditions (n = 6) and in arthritis (n = 8) These data suggest that activation of both NMDA and non-NMDA receptors contributes to pain-related sensitization of amygdala neurons.