UC San Diego

Breathing and pain perception are often investigated as separate behaviors, yet they are tightly connected. For example, severe pain induces hyperventilation, whereas paced slow breathing alleviates perceived pain. Moreover, opioids can reduce pain while resulting in opioid-induced respiratory depression (OIRD), which is the direct cause of death in opioid overdose. Yet, the neurobiological mechanisms of breathing-pain interaction and how their balance is disrupted by opioid overdose are not well understood.This dissertation describes original work investigating the neural circuit mechanisms of how Oprm1 (µ-opioid receptor)-expressing neurons in the lateral parabrachial nucleus (PBL) coordinate breathing with pain and emotions in mice. Exogenous opioids modulate these neurons, which in turn are involved in the expression and rescue of OIRD. Together, these results highlight parabrachial opioidergic pathways as critical nodes for orchestrating breathing and pain, as well as therapeutic candidates for developing side-effect-free painkillers and OIRD treatments.