Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold)

Dicpinigaitis, Peter V.; Tibb, Amit; Ramsey, David; Carr, Andrew N.; Poore, Cathy L.

doi:10.1016/j.pupt.2014.05.004

Cited by 17 publications

(17 citation statements)

References 7 publications

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“…In acute and chronic conditions associated with excessive coughing and enhanced cough reflex sensitivity, for example, inflammation that increases vagal afferent nerve excitability or recruited synaptic inputs that enhance synaptic efficacy at the central terminations of bronchopulmonary vagal afferent nerves may result in cough hypersensitivity and perhaps excessive coughing provoked by only mildly irritating stimuli (e.g., cold air, perfumes) or even to otherwise innocuous stimulants . Such cough hypersensitivity was apparent in the present study in those patients with URIs, with capsaicin C 5 values 2-to 3-fold lower than those observed in healthy subjects, which is consistent with transient, viral URI-induced cough reflex hypersensitivity reported in previous studies (Dicpinigaitis et al, 2014b). Restoring normal cough reflex sensitivity and thus suppressing the excessive coughing associated with disease does not require complete inhibition of vagal afferent nerve activation or a complete suppression of synaptic transmission at the central terminations of the vagal afferents, just a reduction of afferent drive and/or a modest reduction in central synaptic efficacy (Canning, 2009;Canning et al, 2014).…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, those subjects having been randomized to receive memantine first in this crossover trial may still have had significant levels of memantine present at the time of their postplacebo cough reflex sensitivity measurement, thus potentially blunting the difference between the effects of memantine and placebo. The washout period was chosen so as to ensure stability of the cough reflex during the study period, as it has been demonstrated that capsaicin cough reflex sensitivity (C 5 ) remains stable during the first week of URI (Dicpinigaitis et al, 2014b), but stability beyond this time frame has not been confirmed. Despite these shortcomings, this study further substantiates the rationale for NMDA receptor/channel blockade in cough.…”

Section: Discussionmentioning

confidence: 99%

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

Dicpinigaitis

Canning

Garner

et al. 2015

The Journal of Pharmacology and Experimental Therapeutics

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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: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

Dicpinigaitis

Canning

Garner

et al. 2015

The Journal of Pharmacology and Experimental Therapeutics

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“…Colds are usually caused by viral infection; rhinoviruses cause 30% to 50% of colds throughout the year and 80% of colds during peak season, and up to 200 other viruses are implicated [ 2 ]. The main symptoms are sore throat, rhinitis, rhinorrhoea, cough, and malaise [ 1 , 3 , 4 ]. These symptoms typically peak at 1–3 days and last 7–10 days but can persist for several weeks [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi‐Deficiency Syndrome: Study Protocol for a Randomized, Double‐Blind, Placebo‐Controlled, Multicenter, Phase II Clinical Trial

Liu

Fan

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349).

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“…In laboratory animals, viral infections lead to changes in vagal sensory and autonomic neural pathways in manners that could help to explain mechanistically viral-induced increased airway responsiveness [ 6 – 12 ]. The sensitivity to capsaicin-induced cough in subjects and guinea pigs has also been found to increase in the presence of a respiratory tract viral infection, and viral infections can result in a persistent post-viral nagging cough [ 5 , 13 , 14 ]. Here we have focused on potential mechanisms by which respiratory viral infections can lead to such increases in cough sensitivity in guinea pigs.…”

Section: Introductionmentioning

confidence: 99%

Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways

et al. 2016

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The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ “cough receptors” such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli.

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Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold)

Cited by 17 publications

References 7 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

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi‐Deficiency Syndrome: Study Protocol for a Randomized, Double‐Blind, Placebo‐Controlled, Multicenter, Phase II Clinical Trial

Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways

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