The anterior cingulate cortex (ACC) modulates emotional responses to pain. Whereas, the caudal ACC (cACC) promotes expression of pain affect, the rostral ACC (rACC) contributes to its suppression. Both subdivisions receive glutamatergic innervation, and the present study evaluated the contribution of N-methyl-d-aspartic acid (NMDA) receptors within these subdivisions to rats’ expression of pain affect. Vocalizations that follow a brief noxious tail shock (vocalization afterdischarges, VAD) are a validated rodent model of pain affect. The threshold current for eliciting VAD was increased in a dose-dependent manner by injecting NMDA into the rACC, but performance (latency, amplitude, and duration) at threshold was not altered. Alternately, the threshold current for eliciting VAD was not altered following injection of NMDA into the cACC, but its amplitude and duration at threshold were increased in a dose-dependent manner. These effects were limited to Cg1 of the rACC and cACC, and blocked by pretreatment of the ACC with the NMDA receptor antagonist d-2-amino-5-phosphonovalerate. These findings demonstrate that NMDA receptor agonism within the cACC and rACC either increases or decreases emotional responses to noxious stimulation, respectively.

NMDA receptor activation of the rostral and caudal ACC respectively inhibited or enhanced rats’ emotional response to pain. These findings mirror those obtained from human neuroimaging studies; thereby, supporting the use of this model system in evaluating the contribution of ACC to pain affect.