Prostaglandin E2 enhances the sensitizing effect of hyperthermia on pulmonary C-fibers in rats

This study was carried out to investigate whether the pulmonary C-fiber hypersensitivity induced by hyperthermia is altered by prostaglandin E2 (PGE2). Single-unit afferent activities of pulmonary C-fibers were recorded in anesthetized, artificially ventilated rats when the intrathoracic temperature (Tit) was maintained at normal (N; ∼36 °C) and hyperthermia levels (H; ∼41 °C) by perfusion of heated saline into the thoracic chamber for 3 min. After ∼20 min of recovery, the fiber activities were recorded again during infusion of PGE2 at both N and H levels of Tit. Our study showed: (1) The baseline fiber activity and responses to lung inflation, right-atrial injection of capsaicin and adenosine were all increased by increasing Tit from N to H, and these hyperthermia-induced increases in sensitivities were also significantly augmented by PGE2. (2) These enhanced sensitivities induced by PGE2 were abolished by pretreatment with AH6809 and AH23848, selective antagonists of EP2 and EP4 prostanoid receptors, respectively. In conclusion, the hyperthermia-induced hypersensitivity of vagal pulmonary C-fibers is potentiated by PGE2, and this effect is mediated through activation of EP2 and EP4 prostanoid receptors.