Capsaicin challenge, reflex bronchoconstriction, and local action of substance P

Capsaicin was administered as an aerosol to unanesthetized guinea pigs in a whole body plethysmograph and intravenously to anesthetized guinea pigs to investigate its mechanism of action. Capsaicin increased specific airway resistance in the unanesthetized guinea pigs and increased insufflation pressure in anesthetized guinea pigs. To investigate the possible reflex action of capsaicin, an atropine or lidocaine aerosol was administered before the capsaicin aerosol challenge in unanesthetized guinea pigs. Both lidocaine and atropine reduced the effect of capsaicin. However, neither intravenous atropine nor bilateral vagotomy antagonized the effect of injected capsaicin in the anesthetized guinea pigs. To investigate further the possible action of capsaicin, spantide (a substance P receptor antagonist) was administered before capsaicin challenge. Spantide injection in anesthetized guinea pigs attenuated the effects of the intravenous capsaicin challenge. In unanesthetized guinea pigs spantide pretreatment, as an aerosol, did not ameliorate the effects of a capsaicin aerosol challenge. However, intraperitoneal administration of spantide did reduce the effect of the capsaicin aerosol challenge as the specific airway resistance increased. Therefore, capsaicin produced its effects independent of vagal reflexes, although reflex actions of capsaicin could have occurred through other pathways. Reflex actions of capsaicin, however, were demonstrable only in the unanesthetized guinea pig. Because spantide attenuated the effect of capsaicin, increased insufflation pressure and specific airway resistance due to capsaicin challenge in both unanesthetized and anesthetized guinea pigs may be attributed, at least in part, to capsaicin's induction of substance P release or the release of other tachykinins.