Axon reflex in resiniferatoxin-induced bronchoconstriction of guinea pigs.

To study the role of the axon reflex in resiniferatoxin (RTX)-induced bronchoconstriction in vivo, 32 guinea pigs weighing 292 +/- 7 g were randomly divided into five groups: Group 1, control (n = 6); Group 2, chlorisondamine (n = 6); Group 3, tetrodotoxin (TTX, n = 6); Group 4, local capsaicin application (n = 6); and Group 5, systemic capsaicin application (n = 8). Chlorisondamine was used to interrupt ganglionic transmission while TTX was employed to block nerve impulse conduction. In Group 4, capsaicin was locally applied to both cervical vagus nerves 30 min prior to the study whereas capsaicin was given subcutaneously for 5 days starting 9 days before the study in Group 5. Each animal was anesthesized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and artificially ventilated. All the above animals were treated with atropine (0.2 mg/kg) and phenoxybenzamine (0.5 mg/kg). Resiniferatoxin (2 micrograms/kg) was injected intravenously to induce airway constriction. Immediately upon injection of RTX (at 1 min), each animal in the control group exhibited decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, indicating severe bronchoconstriction. Then the airway spasm ameliorated gradually with time. Animals in Groups 3 and 4 indicated partial abolishment, while those in Group 5 showed complete abolishment, of the RTX-induced bronchoconstriction. On the other hand, the animals in Group 2 did not display any significant alteration in the RTX-induced bronchospasm. Furthermore, we tested RTX-induced bronchoconstriction in 5 additional animals not pretreated with either atropine or phenoxybenzamine. Compared with the data above, no significant differences in RTX-induced respiratory changes were found. Since it is known that TTX blocks nerve conduction, the data suggest that the TTX-sensitive reflex (the axon reflex) via afferent C-fibers plays a significant role in the RTX-induced bronchoconstriction, which is apparently mediated via tachykinins.