Amygdala physiology in pain

The amygdala has emerged as an important brain area for the emotional-affective dimension of pain and pain modulation. The amygdala receives nociceptive information through direct and indirect routes. These excitatory inputs converge on the amygdala output region (central nucleus) and can be modulated by inhibitory elements that are the target of (prefrontal) cortical modulation. For example, inhibitory neurons in the intercalated cell mass in the amygdala project to the central nucleus to serve gating functions, and so do inhibitory (PKCdelta) interneurons within the central nucleus. In pain conditions, synaptic plasticity develops in output neurons because of an excitation-inhibition imbalance and drives pain-like behaviors and pain persistence. Mechanisms of pain related neuroplasticity in the amygdala include classical transmitters, neuropeptides, biogenic amines, and various signaling pathways. An emerging concept is that differences in amygdala activity are associated with phenotypic differences in pain vulnerability and resilience and may be predetermining factors of the complexity and persistence of pain.