Central pathways for cough in man--unanswered questions

Central processing of afferent cough impulses occurs in a putative 'cough centre' in the dorsal medulla where the reflex is subject to considerable cortical control. Little is known about the central neurotransmitters and mediators which mediate cough in humans. Previous animal and human studies suggest that the antitussive effect of opiates may be mediated at central 5-HT receptors. In three studies in healthy human volunteers, we have investigated the potential role of central cholinergic and dopaminergic receptors in the mediation of cough, and the potential role of 5-HT receptors in the antitussive action of opiates. Intravenous administration of atropine or physostigmine had no effect on capsaicin-induced cough. Similarly, oral administration of L-dopa, bromocriptine or haloperidol had no effect on capsaicin-induced cough. Compared with saline, intravenous morphine significantly suppressed capsaicin-induced cough and increased drowsiness. Compared with placebo, pretreatment with oral pizotifen significantly attenuated the antitussive effect of morphine, but not the sedative effect. This suggests that in humans, an agonist action at 5-HT2 and/or 5-HT1 receptors may be involved in the antitussive effect of morphine, but not its sedative effect. Further knowledge of central cough pathways in humans must await the availability of more selective receptor agonists and antagonists for human studies. This offers the promise of effective antitussive therapy. The challenge is to find an antitussive agent which can return the abnormal sensitivity of the cough reflex to normal, without adverse effects.