Central sensitization of the spino-parabrachial-amygdala pathway that outlasts a brief nociceptive stimulus.

Pain is an important defence against dangers in our environment; however, some clinical conditions produce pain that outlasts this useful role and persists even after the injury has healed. The experience of pain consists of somatosensory elements of intensity and location, negative emotional/aversive feelings and subsequent restrictions on lifestyle as a result of a learned association between certain activities and pain. The amygdala contributes negative emotional value to nociceptive sensory information and forms the association between an aversive response and the environment in which it occurs. It is able to form this association because it receives nociceptive information via the spino-parabrachio-amygdaloid pathway and polymodal sensory information via cortical and thalamic inputs. Synaptic plasticity occurs at the parabrachial-amygdala synapse and other brain regions in chronic pain conditions with ongoing injury; however, very little is known about how plasticity occurs in conditions with no ongoing injury. Using immunohistochemistry, electrophysiology and behavioural assays, we show that a brief nociceptive stimulus with no ongoing injury is able to produce long-lasting synaptic plasticity at the rat parabrachial-amygdala synapse. We show that this plasticity is caused by an increase in postsynaptic AMPA receptors with a transient change in the AMPA receptor subunit, similar to long-term potentiation. Furthermore, this synaptic potentiation primes the synapse so that a subsequent noxious stimulus causes prolonged potentiation of the nociceptive information flow into the amygdala. As a result, a second injury could have an increased negative emotional value and promote associative learning that results in pain-related avoidance.