The amygdala is generally considered a brain center for emotions. In pain models, synaptic plasticity develops in a network of lateral (LA), basolateral (BLA) and central (CeA) nuclei. The resulting hyperactivity of CeA neurons drives amygdala-dependent pain behaviors such as emotional-affective responses (vocalizations) and anxiety. Hyperactivity of BLA neurons inhibits processing in the medial prefrontal cortex (mPFC) through “feedforward inhibition”, resulting in cognitive deficits such as impaired decision-making. Counteracting abnormal inhibition of mPFC output neurons mitigates cognitive deficits and also inhibits pain behaviors. At least part of this beneficial effect involves cortical inhibition of amygdala neurons, suggesting that strategies to restore cortical control may have therapeutic value.