Role of the axon reflex in capsaicin-induced bronchoconstriction in guinea pigs

To study the axon reflex as a contributing factor to capsaicin-induced bronchoconstriction in vivo, 30 guinea pigs weighing 325 +/- 7 g were randomly divided into four groups: Group 1, control (n = 6); Group 2, bupivacaine (n = 11); Group 3, tetrodotoxin (TTX, n = 10); and Group 4, tachykinin depletion (n = 3). Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and artificially ventilated. All animals were treated with atropine and phenoxybenzamine, and a ganglionic blocking agent (chlorisondamine) was given to about half of the animals. Capsaicin (16 micrograms/kg) was intravenously injected to induce bronchoconstriction. Immediately upon the capsaicin being induced each animal exhibited a decrease in vital capacity, maximal expiratory flow and respiratory compliance, as well as a more than six-fold increase in residual volume, indicating severe bronchoconstriction. Then, the airway spasm decreased gradually toward the baseline values. The animals in Group 4 indicated a complete abolishment of the capsaicin-induced bronchoconstriction, whereas Group 2 and Group 3 displayed a significantly attenuated constriction at 15 to 20 min after capsaicin injection. Administration of chlorisondamine did not alter the capsaicin-induced bronchospasm. Since it is known that bupivacaine and TTX block nerve conduction, the data suggest that the axon reflex plays a significant role in the late phase of bronchoconstriction, which is apparently mediated via tachykinins.