Opioids differentially modulate two synapses important for pain processing in the amygdala.

BACKGROUND AND PURPOSE

Pain is a subjective experience involving sensory discriminative and emotionally aversive components. Consistent with its role in pain processing and emotions, the amygdala modulates the aversive component of pain. The laterocapsular region of the central nucleus of the amygdala (CeLC) receives nociceptive information from the parabrachial nucleus (PB) and polymodal, including nociceptive, inputs from the basolateral nucleus of the amygdala (BLA). Opioids are strong analgesics and reduce both the sensory discriminative and the affective component of pain. However, it is unknown whether opioids regulate activity at the two nociceptive inputs to the amygdala.

EXPERIMENTAL APPROACH

Using whole-cell electrophysiology, optogenetics, and immunohistochemistry, we investigated whether opioids inhibit the rat PB-CeLC and BLA-CeLC synapses.

KEY RESULTS

Opioids inhibited glutamate release at the PB-CeLC and BLA-CeLC synapses. Opioid inhibition is via the μ-receptor at the PB-CeLC synapse, while at the BLA-CeLC synapse, inhibition is via μ-receptors in all neurons and via δ-receptors and κ-receptors in a subset of neurons.

CONCLUSIONS AND IMPLICATIONS

Agonists of μ-receptors inhibited two of the synaptic inputs carrying nociceptive information into the laterocapsular amygdala. Therefore, μ-receptor agonists, such as morphine, will inhibit glutamate release from PB and BLA in the CeLC, and this could serve as a mechanism through which opioids reduce the affective component of pain and pain-induced associative learning. The lower than expected regulation of BLA synaptic outputs by δ-receptors does not support the proposal that opioid receptor subtypes segregate into subnuclei of brain regions.