The Amygdala as a Master Generator of Pain Plasticity – from Nociceptive Amygdala to Nociplastic Amygdala

For more than three decades, the amygdala has been at the forefront of neurophysiological studies to elucidate how pain affects brain networks. First, researchers found that neurons in the central amygdala (CeA) receive "nociceptive" inputs with a relay at the parabrachial nucleus (PBN) from the spinal and medullary dorsal horn and that CeA responses are sensitized in persistent pain conditions. Then, in isolated brain slice preparations, researchers revealed that different types of pain induce robust synaptic plasticity in the CeA. Subsequent biochemical and pharmacological studies demonstrated a causal function of the CeA in the modulation of pain-related behaviors. Besides, human imaging studies revealed morphofunctional alterations in the amygdala in patients with chronic pain. This workshop will update on neurobiological mechanisms and behavioral outcomes of the "nociplastic amygdala," i.e., producing and promoting pain in the presence and even absence of nociception and tissue pathology through neuroplasticity. Results from opto- and chemogenetic approaches combined with molecular techniques to study individual amygdala neuron types and associated circuits that serve different functions in different stages of pain will be presented. The audience will benefit from discussing novel concepts and approaches to brain plasticity as a pain mechanism.