Investigation of the urge‐to‐cough sensation in healthy volunteers

Dicpinigaitis, Peter V.; Rhoton, William; Bhat, Rajani; Negassa, Abdissa

doi:10.1111/j.1440-1843.2011.02094.x

Cited by 26 publications

(16 citation statements)

References 20 publications

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“…These pharmacological properties of NMDA receptors predict their involvement in cough. Thus, induced cough in humans is preceded by an initial urge to cough (Davenport et al, 2007;Dicpinigaitis et al, 2012), an observation that is likely the clinical manifestation of the physiologic evidence that cough initiation requires sustained, high-frequency vagal afferent nerve activation in animals (Canning, 2009;Canning and Mori, 2011). Consistent with the involvement of NMDA receptors in cough, both ketamine and dextromethorphan have been reported to suppress cough in patients (Yeh et al, 2007;Faruqi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effect of Memantine on Cough Reflex Sensitivity: Translational Studies in Guinea Pigs and Humans

Dicpinigaitis

Canning

Garner

et al. 2014

J Pharmacol Exp Ther

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Cough is the most common complaint for which outpatients in the United States seek medical attention, and yet available therapeutic options for cough lack proven efficacy and are further limited by safety and abuse liabilities. Thus, safe and effective cough suppressants are needed. Recent preclinical studies described the antitussive effects of memantine, an N-methyl-D-aspartate receptor channel blocker used in the treatment of Alzheimer's disease. The goals of the present study were to compare the antitussive effects of memantine, dextromethorphan, and codeine in guinea pigs; to relate the dosedependent actions of memantine in these studies to peak plasma concentrations achieved following oral administration; and to provide the first ever evaluation of the antitussive effect of memantine in humans. In guinea pigs, memantine and codeine were comparable in efficacy and potency but both were superior to dextromethorphan in the citric acid cough challenge model. The pharmacokinetic analyses suggest that memantine was active in guinea pigs at micromolar plasma concentrations. Subsequently, 14 healthy volunteers as well as 14 otherwise healthy adults with acute viral upper respiratory tract infection (URI) underwent capsaicin cough challenges 6 hours after ingestion of 20 mg memantine and matched placebo in a randomized, double-blind, crossover fashion. In healthy volunteers, memantine significantly inhibited cough reflex sensitivity (P 5 0.034). In subjects with URI, responsiveness to capsaicin was markedly increased, and in these patients, the inhibition of cough reflex sensitivity by memantine relative to placebo did not reach statistical significance (P 5 0.088). These data support further research to investigate the potential of memantine as a clinically useful antitussive.

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Section: Discussionmentioning

confidence: 99%

Effect of Memantine on Cough Reflex Sensitivity: Translational Studies in Guinea Pigs and Humans

Dicpinigaitis

Canning

Garner

et al. 2014

J Pharmacol Exp Ther

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“…However, it is difficult to measure it accurately, because it is an exclusively subjective phenomenon. We used the method described by Dicpinigaitis et al [18], we estimated Cu - the first concentration of capsaicin aerosol which induced urge to cough, and we asked our subjects to evaluate and compare verbally the feelings regarding the urge to cough after each capsaicin inhalation.…”

Section: Methodsmentioning

confidence: 99%

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels

Buday

Brozmanová

Biringerová

et al. 2012

Cough

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BackgroundCough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. In animal models, modulation of cough by nasal afferent inputs can either facilitate or inhibit the cough response, depending on the type of trigeminal afferents stimulated.MethodsIn this study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with isocyanate (AITC), cinnamaldehyde, (−) menthol and (+) menthol (all 10-3 M) nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response were measured).ResultsNasal challenges with TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p<0.05) but no statistically significant modulation of the C2 and cumulative cough response. In contrast, both TRPM8 agonists administered to the nose significantly modulated all parameters including C2 (p<0.05), Cu (p<0.01) and cumulative cough response (p <0.01) documenting strong anti irritating potential of menthol isomers.ConclusionsIn addition to trigeminal afferents expressing TRP channels, olfactory nerve endings, trigemino – olfactoric relationships, the smell perception process and other supramedullar influences should be considered as potential modulators of the cough response in humans.

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“…The urge‐to‐cough threshold was defined as the initial concentration of citric acid which induced the urge‐to‐cough sensation without a preceding motor cough event and was termed C u (Dicpinigaitis et al. ).…”

Section: Methodsmentioning

confidence: 99%

Gender differences in the effect of urge-to-cough and dyspnea on perception of pain in healthy adults

et al. 2014

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Previous studies have reported that respiratory sensations, such as urge‐to‐cough and dyspnea, have an inhibitory effect on pain. Considering the existence of gender differences in both urge‐to‐cough and pain, it is conceivable that a gender difference also exists in the analgesia induced by urge‐to‐cough. In this study, we evaluated gender differences in the pain perception response to urge‐to‐cough, as well as to dyspnea. Twenty‐seven male and 26 female healthy nonsmokers were originally enrolled. Citric acid challenge was used to induce the urge‐to‐cough sensation, and dyspnea was elicited by inspiratory loaded breathing. Before and during inductions of these two respiratory sensations, perception of pain was assessed by the thermal pain threshold, and differences between men and women were compared. The thermal pain threshold in women (43.83 ± 0.17°C) was significantly lower than that in men (44.75 ± 0.28°C; P < 0.05) during the baseline period. Accompanying increases in both citric acid concentration and inspiratory resistive load, thermal pain threshold values significantly increased in both men and women. The average thermal pain threshold changes for comparable increases in the urge‐to‐cough Borg score were parallel between men and women. Furthermore, the mean value of the thermal pain threshold plotted against the dyspnea Borg score also showed no significant gender difference. These results demonstrate that although gender differences exist in respiratory sensations, that is, urge‐to‐cough and dyspnea, the inhibitory effects of these respiratory sensations on the perception of pain are not significantly different between the sexes.

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Investigation of the urge‐to‐cough sensation in healthy volunteers

Cited by 26 publications

References 20 publications

Effect of Memantine on Cough Reflex Sensitivity: Translational Studies in Guinea Pigs and Humans

Effect of Memantine on Cough Reflex Sensitivity: Translational Studies in Guinea Pigs and Humans

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels

Gender differences in the effect of urge-to-cough and dyspnea on perception of pain in healthy adults

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