Inhibitory control of the cough reflex by galanin receptors in the caudal

26 The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related 27 afferents and a strategic site for the modulation of the cough reflex. The similarities 28 between the characteristics of central processing of nociceptive and cough-related inputs 29 led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, 30 could also be involved in the regulation of the cough reflex at the level of the NTS, 31 where galanin receptors have been found. We investigated the effects of galanin and 32 galnon, a non-peptide agonist at galanin receptors, on cough responses to mechanical 33 and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were 34 microinjected (30-50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, 35 spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the 36 mechanical stimulation of the airway mucosa via a custom-built device were also 37 investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough 38 number, peak abdominal activity, and increased cough-related total cycle duration. 39 Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, 40 whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects 41 consistent with those produced by galanin. Galnon effects were confirmed by using the 42 cough-inducing device. The results indicate that galanin receptors play a role in the 43 inhibitory control of the cough reflex at the level of the caudal NTS and provide hints 44 for the development of novel antitussive strategies. 45 46