Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs

Hara, Johsuke; Fujimura, Masaki; Myou, Shigeharu; Oribe, Yoshitaka; Furusho, Shiho; Kita, Toshiyuki; Katayama, Nobuyuki; Abo, Masahiro; Ohkura, Noriyuki; Herai, Yoriko; Hori, Akihiro; Ishiura, Yoshihisa; Nobata, Kouichi; Ogawa, Haruhiko; Yasui, Masahide; Kondo, Kazuo; Nakao, Shinji

doi:10.1186/1745-9974-1-6

Cited by 11 publications

(5 citation statements)

References 23 publications

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“…In addition, it has been shown that both the NK 1 receptor antagonist FK888 and the dual NK 1 and NK 2 peptide receptor antagonists FK224 significantly inhibited the increase in cough response to inhaled capsaicin in different types of guinea pig models of cough with allergic airway inflammation [31][32][33]. In our laboratory, we previously showed in the actively sensitized guinea pigs that the increase in the cough reflex sensitivity after an antigen challenge is correlated with increase in the SP levels in the BALF [18] and the decrease in the NEP activity in the tracheal tissue [19], which are consistent with the results in the present study. Taken together, these findings suggest that the role of peripheral SP in cough reflex sensitivity may be different between species and/or employed experimental systems, especially presence of airway inflammation.…”

Section: Discussionmentioning

confidence: 87%

“…Thirty minutes later, the conscious guinea pigs were challenged for 90 seconds with 10 mg/ml OA aerosol by a method described previously [6,18,19]. The animals in the NC group were not injected with diphenhydramine, but they did inhale aerosolized saline by the same method as that described for the sensitized guinea pigs.…”

Section: Antigen Challengementioning

confidence: 99%

“…BAL was performed immediately after analyzing the cough reflex sensitivity to capsaicin by a method as described previously [18,19]. Briefly, the guinea pigs were anaesthetized by the intraperitoneal injection of 75 mg/kg of sodium pentobarbital and they were placed in a supine position.…”

Section: Bronchoalveolar Lavage (Bal)mentioning

confidence: 99%

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Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

Tokuda¹,

Ohkura²,

Fujimura³

et al. 2010

Pulmonary Pharmacology & Therapeutics

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Hence, they are used for both acute and chronic inflammatory airway diseases.However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated.Objective: To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. Methods:The cough reflex sensitivity to inhaled capsaicin was measured at 48 h after challenge with an aerosolized antigen in actively sensitized guinea pigs.The 14-, 15-or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12 h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. Results:The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E 2 and leukotriene B 4 levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue.Conclusions: Both 14-and 15-membered, but not 16-membered, macrolides 3 could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough.

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Section: Discussionmentioning

confidence: 87%

Section: Antigen Challengementioning

confidence: 99%

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Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

Tokuda¹,

Ohkura²,

Fujimura³

et al. 2010

Pulmonary Pharmacology & Therapeutics

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“…Animals were administered 1 ml of a 50 mg/ml ovalbumin (Ova) in 0.9% w/v saline solution via the intraperitoneal route and 0.5 ml of the same solution into two separate subcutaneous sites (1 ml in total divided between the left and right flank). All animals were administered a single intraperitoneal dose of pyrilamine (15 mg·kg ‐1 ) at a dose volume of 1 ml·kg ‑1 approximately 30 min prior to ovalbumin challenge on Day 14 to inhibit histamine‐induced bronchospasm (Featherstone et al, 1988; Hara et al, 2005). On Day 14, animals were challenged with aerosolized ovalbumin in 0.9% w/v saline (3 mg·ml ‐1 ) or 0.9% w/v saline for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker

Tochitsky

Andrews

et al. 2021

British J Pharmacology

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Background and Purpose Many pain‐triggering nociceptor neurons express TRPV1 or TRPA1, cation‐selective channels with large pores that enable permeation of QX‐314, a cationic analogue of lidocaine. Co‐application of QX‐314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW‐031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough. Experimental Approach We tested the ability of BW‐031 to inhibit pain in three models of tissue inflammation:‐ inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW‐031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. Key Results BW‐031 inhibited Nav1.7 and Nav1.1 channels with approximately sixfold greater potency than QX‐314 when introduced inside cells. BW‐031 inhibited inflammatory pain in all three models tested, producing more effective and longer‐lasting inhibition of pain than QX‐314 in the mouse UV burn model. BW‐031 was effective in reducing cough counts by 78%–90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization. Conclusion and Implications BW‐031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW‐031 can also effectively inhibit cough in a guinea pig model of citric acid‐induced cough, suggesting a new clinical approach to treating cough.

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“…Animals were administered 1 mL of a 50 mg/mL Ovalbumin (Ova) in 0.9% w/v saline solution via the intraperitoneal route and 0.5 mL of the same solution into 2 separate subcutaneous sites (1 mL in total divided between the left and right flank). All animals were administered a single intraperitoneal dose of pyrilamine (15 mg/kg) at a dose volume of 1 mL/kg approximately 30 min prior to ovalbumin challenge on Day 14 to inhibit histamine-induced bronchospasm (Featherstone et al, 1988;Hara et al, 2005). On Day 14 animals were challenged with aerosolised ovalbumin in 0.9% w/v saline (3 mg/mL) or 0.9% w/v saline for 15 min.…”

Section: Guinea Pig Cough Experimentsmentioning

confidence: 99%

Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker

Tochitsky

Andrews

et al. 2021

Preprint

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Background and Purpose: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. We now describe BW-031, a novel more potent cationic sodium channel inhibitor, test whether its application alone can inhibit the pain associated with tissue inflammation, and whether this strategy can also inhibit cough. Experimental Approach: We characterized BW-031 inhibition of sodium channels and tested BW-031 in three models of inflammatory pain: rat paw inflammation produced by Complete Freund’s Adjuvant injection or surgical incision and a mouse paw UV burn model. We also tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. Key Results: BW-031 inhibited Nav1.7 and Nav1.1 channels with ~6-fold greater potency than QX-314 when introduced inside cells and entered capsaicin-activated TRPV1 expressing sensory neurons. BW-031 inhibited inflammatory pain in all three models, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was also effective in reducing cough counts by 78-90% when applied intratracheally under isoflurane anesthesia or by aerosol inhalation in awake guinea pigs with airway inflammation produced by ovalbumin sensitization. Conclusion and Implications: BW-031 a novel cationic sodium channel inhibitor can be applied locally as a single agent to inhibit inflammatory pain and also effectively inhibits cough in a guinea pig model of nociceptor-activated cough, suggesting a new clinical approach to treating cough.

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Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs

Cited by 11 publications

References 23 publications

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker

Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker

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