Abstract
Chronic pain is a major public health problem, leading to long term disability and distress that makes its clinical management challenging. Central amygdala (CeA) is a key neural substrate that contributes in the control of the pain response and modulates the affective-motivational component of pain. It is known that PKCδ (+) neurons in latero-capsular region of CeA (CeLC) is a dominant direct recipient of parabrachial inputs, constituting a pathway that has been implicated in pain. However, molecular mechanisms at PB-CeLC synapses driving nociception remains unclear. In present study, we demonstrate the role of synaptic organizer glutamate receptor delta 1 (GluD1), uniquely enriched in CeLC, in pain behaviors. We demonstrate that deletion of amygdalar GluD1 leads to impairment in parabrachio-amygdalar neurotransmission. However, in condition of pain, somatic GluD1 and its synaptic partners in CeA undergoes significant downregulation with surface upregulation of AMPA subunit. Interestingly, exogenous application of protein therapeutic is able to alleviate pain induced mechanical hypersensitivity by restoring the GluD1 levels. This report will open a new arena of using protein therapeutics in modulating pain phenotypes and serve as a potential alternative to existing line of treatment.