A parabrachial-to-amygdala circuit that determines hemispheric lateralization of somatosensory processing

Abstract

Background: The central amygdala (CeA) is a bilateral hub of pain and emotional processing with well-established functional lateralization. We reported that optogenetic manipulation of neural activity in the left and right CeA has opposing effects on bladder pain. Methods: To determine the influence of calcitonin gene-related peptide (CGRP) signaling from the parabrachial nucleus (PBN) on this diametrically opposed lateralization, we administered CGRP and evaluated the activity of CeA neurons in acute brain slices as well as the behavioral signs of bladder pain in the mouse. Results: We found that CGRP increased firing in both the right and left CeA neurons. Furthermore, we found that CGRP administration in the right CeA increased behavioral signs of bladder pain and decreased bladder pain-like behavior when administered in the left CeA. Conclusions: These studies reveal a parabrachial-to-amygdala circuit driven by opposing actions of CGRP that determines hemispheric lateralization of visceral pain.

The parabrachial to central amygdala circuit is a key mediator of injury-induced pain sensitization

“…Maladaptive plasticity in the PbN→CeA pathway has also been proposed to contribute to persistent hypersensitivity in pathological conditions (18,26), no longer serving a protective function. Consistent with this idea, recent work demonstrated that CGRP signaling in the right PbN→CeA pathway contributes to bladder pain-like behaviors but not pain-related aversion in a mouse model of cystitis (67). The results in the present study expand on these previous findings to show that the PbN→CeA pathway is also a major contributor of hypersensitivity to peripheral stimulation in response to inflammation or nerve injury.…”