Airway nociceptors activated by pro-inflammatory cytokines

The present studies evaluate whether the vagus nerves link the lungs’ immune and neural systems by transmitting information through pulmonary nociceptors. Single unit activities from pulmonary nociceptors [C fiber receptors (CFRs) and high threshold Aδ fiber receptors (HTARs)] were recorded from the cervical vagus nerve in anesthetized, open-chest, and mechanically ventilated rabbits. Interleukin1β was then injected into the nociceptor field (IL-1β, 10 μg/ml, 20 μl). Both CFRs and HTARs were stimulated by the local injection; their activities increased from 0.2 ± 0.1 to 1.8 ± 0.5 imp/s (n = 10; p < 0.01), and from 0.2 ± 0.1 to 1.1 ± 0.1 imp/s, respectively (n = 6; p < 0.01). These increases were greatly attenuated by simultaneous administration of IL-1β with IL-1ra, a natural IL-1 receptor antagonist. The nociceptors were not stimulated by local injection of normal saline. Our data demonstrate that nociceptors can be activated by pro-inflammatory cytokines and support the hypothesis that airway nociceptors transmit immune signals from the lung to the brain.