The Difference in Citric Acid-Induced Cough in Congenitally Bronchial-Hypersensitive (BHS) and Bronchial-Hyposensitive (BHR) Guinea Pigs.

Yagi, Yuki; Kuwahara, Masayoshi; Nanji, Atsumi; Birumachi, Jun-ichi; Nishibata, Ryoji; Mikami, Hiroki; Tsubone, Hirokazu

doi:10.1538/expanim.50.371

Cited by 7 publications

(9 citation statements)

References 29 publications

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“…These results suggest that capsaicin and citric acid induce coughs by a similar mechanism (possibly through the capsaicin-sensitive C-fibers). This finding is in agreement with that of a previous study (11). Microinjection of capsaicin into the larynx induced approximately 100-fold weaker responses than inhalation, whereas microinjection of citric acid induced approximately 3-fold larger responses than inhalation.…”

Section: Discussionsupporting

confidence: 93%

“…The following drugs were preadministered 15 min before the injection to counteract the respiratory impairment associated with capsaicin injection: atropine sulfate (1 mg/ kg, s.c.), terbutaline (0.1 mg /kg, s.c.), and aminophylline (25 mg / kg, i.p.). These animals were used for experiments 1 week after the last capsaicin pretreatment (11).…”

Section: Capsaicin Pretreatmentmentioning

confidence: 99%

“…Previously, we developed a coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized unrestrained guinea pigs, without inducing sneezes (9,10). Here, we compared the responses to capsaicin or citric acid before and after chemical enervation of C-fibers (pretreatment with capsaicin 100 mg / kg, s.c.) (11) and examined the roles of the Aδ-fibers and C-fibers in the larynx area.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Tanaka

Maruyama

2005

J Pharmacol Sci

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Abstract. Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 µM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean ± S.E.M.: 8.85 ± 1.60 and 10.40 ± 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 µl in total in 10 aliquots of 2 µl at 30-s intervals) induced 27.29 ± 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 ± 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg / kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer nonmyelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Aδ-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Aδ-fibers.

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Section: Discussionsupporting

confidence: 93%

Section: Capsaicin Pretreatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Tanaka

Maruyama

2005

J Pharmacol Sci

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“…It may enable us to determine how acidity (such as citric acid-induced cough) affects both hyper- and hyposensitive individuals. In bronchial hypersensitive and bronchial hyposensitive guinea pigs, exposure to citric acid for 10 min increased the frequency and latency of cough to a greater extent in the bronchial hypersensitive than in the bronchial hyposensitive guinea pigs; this effect could be desensitized by pretreatment with atropine, lidocaine, salbutamol, or capsaicin [22]. …”

Section: Discussionmentioning

confidence: 99%

Acute Local Tolerability of Acidic Aqueous Vehicles Delivered via Respimat® Soft Mist™ Inhaler in Hyperreactive Asthma Patients

Leclerc¹,

Lafferre

Pavia

2007

Respiration

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Background:Acidic inhalers can be associated with increased adverse reactions. Objectives: This study aimed to determine the acute local tolerability of acidic aqueous placebo formulations delivered via Respimat® Soft Mist™ Inhaler (SMI) and placebo chlorofluorocarbon metered dose inhaler (CFC-MDI).Methods: A single-dose (four inhalations), randomized, double-blind within Respimat SMI device, four-way crossover study in asthma patients with documented bronchial hyperresponsiveness was used. Patients received acidic placebo solutions [pH 2.7, 3.4 or 7.0 (neutral)], delivered via Respimat SMI or placebo CFC-MDI. The primary endpoint was the largest decrease in forced expiratory volume in 1 s (FEV₁) from baseline to 0–30 min after dosing. Secondary endpoints included spirometry, paradoxical bronchoconstriction (defined as a fall in FEV₁ ≧15% below baseline within 30 min of dosing), cough episodes and adverse events.Results: Thirty-two patients were included in the per-protocol population (mean age 27 years, 62.5% males). The mean percentage decrease in FEV₁ was comparable between treatment groups: –1.6% (Respimat SMI pH 2.7), –1.8% (Respimat SMI pH 7.0), –1.9% (CFC-MDI), and –2.3% (Respimat SMI pH 3.4); no patient experienced paradoxical bronchoconstriction. The mean number of cough episodes was significantly lower in the Respimat SMI pH 2.7 group versus CFC-MDI (p = 0.0165). No patient used rescue medication. Only 3 patients experienced at least one adverse event. Conclusions: The Respimat SMI pH 2.7 placebo solution does not induce adverse events in these patients. Compared with the CFC-MDI placebo suspension, Respimat SMI is a well-tolerated inhaled medication delivery system that can accommodate medication formulations with a wide range of pH solutions.

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“…A total dose of 100 mg/kg of capsaicin was divided into 4 portions (10, 20, 30, and 40 mg/kg) and subcutaneously injected over 4 days. Fifteen minutes before each dose of capsaicin, the animals received atropine sulfate (1 mg/kg i. p.) and aminophylline (25 mg/kg i. p.) to minimize its irritating effect [22]. The animals which survived the pretreatment were tested for capsaicin-induced cough to confirm successful capsaicin desensitization 1 week after the last capsaicin pretreatment (the method was the same as described in experiment 4).…”

Section: Methodsmentioning

confidence: 99%

Antitussive Effect of Naringin on Experimentally Induced Cough in Guinea Pigs

Gao

Yang

et al. 2010

Planta Med

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The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels.

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The Difference in Citric Acid-Induced Cough in Congenitally Bronchial-Hypersensitive (BHS) and Bronchial-Hyposensitive (BHR) Guinea Pigs.

Cited by 7 publications

References 29 publications

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Acute Local Tolerability of Acidic Aqueous Vehicles Delivered via Respimat® Soft Mist™ Inhaler in Hyperreactive Asthma Patients

Antitussive Effect of Naringin on Experimentally Induced Cough in Guinea Pigs

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