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 (T_it) 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 T_it. 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 T_it 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.