Most vagal sensory afferents innervating the lower airways are activated by noxious stimuli including irritants and inflammatory mediators, causing nociceptive cardiorespiratory reflexes (e.g. cough, bronchospasm, changes in respiratory drive and heart rate). Vagal ganglia are comprised of embryologically distinct nodose and jugular neurons, but little is known of their specific contribution to nociceptive reflexes. Here, we mapped and modulated distinct nociceptive afferents using an intersectional genetics approach. TRPV1+P2X2+ neurons were found exclusively in the nodose ganglion. TRPV1+P2X2+ fibers innervated the lungs with many projected into the alveoli. Centrally, they innervated the nucleus tractus solitarius (nTS). >90% of TRPV1+Tac1+ neurons were found in the jugular ganglion. TRPV1+Tac1+ fibers innervated the lungs, but none projected into the alveoli. Centrally, they terminated solely in the paratrigeminal complex (Pa5). Many TRPV1–Tac1+ neurons were found in both nodose and jugular ganglia that innervated the large pulmonary airways. These projected to both nTS and Pa5. Using intersectional chemogenetics, we selectively stimulated lower airway afferent subsets using intravenous injections of clozapine-N-oxide (CNO). Activation of TRPV1+, TRPV1+P2X2+ or TRPV1+Tac1+ fibers evoked bradycardia and bradypnea. Activation of Tac1+ and vagal TRPV1–Tac1+ fibers evoked tachycardia and/or tachypnea. These data show the distinct innervation patterns and reflex function of multiple nociceptive vagal afferent subsets. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Thomas Taylor-Clark (Fri,) studied this question.