Multiple Neural Networks Originating from the Lateral Parabrachial Nucleus Modulate Cough-like Behavior and Coordinate Cough with Pain

It has been reported that experimental pain can diminish cough sensitivity and that the lateral parabrachial nucleus (LPBN) coordinates pain with breathing, but whether the LPBN regulates cough-like behaviors and pain-induced changes in cough sensitivity remains elusive. We investigated the roles of LPBN γ-aminobutyric acidergic (GABAergic) and glutamatergic neurons in the regulation of cough sensitivity and its relationship with pain in mice via chemogenetic approaches. Adenovirus-associated virus tracing combined with chemogenetics was used to map the projections of LPBN GABAergic and glutamatergic neurons to the periaqueductal gray. LPBN neurons were activated by cough challenge, and nonspecific inhibition of LPBN neurons suppressed cough-like behavior. Chemogenetic suppression of LPBN GABAergic neurons reduced cough sensitivity in mice, whereas suppression of LPBN glutamatergic neurons counteracted the pain-driven decrease in cough sensitivity, and so did silencing LPBN glutamatergic neurons projecting to the periaqueductal gray. Our data suggest that GABAergic and glutamatergic neurons in the LPBN critically are involved in cough sensitivity and coordinate pain with cough through inhibitory or activating mechanisms at the midbrain level.