Capsaicin stimulates mucociliary activity by releasing substance P and acetylcholine.

Intraarterial injection of the neuropeptide substance P (SP) accelerates mucociliary (MC) activity. The physiological significance of this finding was investigated using capsaicin, which is known to release SP from unmyelinated C-fibers in sensory nerves. Capsaicin (3.0-150.0 micrograms/kg) stimulated MC activity in the rabbit maxillary sinus in vivo, recorded with a photoelectric technique. This effect was resistant to pretreatment with the adrenergic blocker guanethidine, and to a combination of propranolol and phentolamine. Pretreatment with an SP antagonist (D-Pro2, D-Trp7,9)SP totally inhibited the effect of capsaicin. The muscarinic antagonist atropine suppressed the initial phase of the response to capsaicin, whereas the response was uniformly suppressed by the ganglionic blocker hexamethonium. These results suggest that capsaicin activates a reflex, via afferent C-fibers containing SP and efferent parasympathetic cholinergic neurons. The final response of the MC system reflects the local release of both SP and acetylcholine.