Animal models of cough

Plevková, Jana; Brozmanová, Mariana; Matloobi, Alireza; Poliaček, Ivan; Honetschlager, Jan; Buday, Tomáš

doi:10.1016/j.resp.2021.103656

Cited by 13 publications

(17 citation statements)

References 106 publications

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“…As discussed above, the afferent innervation of the mouse lung is somewhat different to that of other mammals such as the guinea pig – in particular the contribution by TRPV1-negative C fibers. Mice also lack a major nodose Aδ fiber subset that innervates the trachea ( Hennel et al, 2018 ; Kim et al, 2020a ), and mice lack a cough reflex to canonical tussive stimuli ( Plevkova et al, 2021 ) and have limited neurogenic inflammatory responses ( Baluk et al, 1999 ). Nevertheless, the genetic tools available for the mouse provide anatomically relevant information regarding distinct nociceptive and non-nociceptive subsets whose activation evokes specific respiratory and cardiovascular reflexes ( Coleridge and Coleridge, 1984 ; Mazzone and Undem, 2016 ; Taylor-Clark, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Kim

Patil

Hadley

et al. 2022

eNeuro

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The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g., cough, bronchospasm). Airway innervation is heterogeneous, and distinct afferent subsets have distinct functional responses. However, little is known of the innervation patterns of subsets within the lung. A neuroanatomical map is critical for understanding afferent activation under physiological and pathophysiological conditions. Here, we quantified the innervation of the mouse lung by vagal and dorsal root ganglion (DRG) sensory subsets defined by the expression of Pirt (all afferents), 5HT 3 (vagal nodose afferents), Tac1 (tachykinergic afferents), and transient receptor potential vanilloid 1 channel (TRPV1; defensive/nociceptive afferents) using Cre-mediated reporter expression. We found that vagal afferents innervate almost all conducting airways and project into the alveolar region, whereas DRG afferents only innervate large airways. Of the two vagal ganglia, only nodose afferents project into the alveolar region, but both nodose and jugular afferents innervate conducting airways throughout the lung. Many afferents that project into the alveolar region express TRPV1. Few DRG afferents expressed TRPV1. Approximately 25% of blood vessels were innervated by vagal afferents (many were Tac1+). Approximately 10% of blood vessels had DRG afferents (some were Tac1+), but this was restricted to large vessels. Lastly, innervation of neuroepithelial bodies (NEBs) correlated with the cell number within the bodies. In conclusion, functionally distinct sensory subsets have distinct innervation patterns within the conducting airways, alveoli and blood vessels. Physiologic (e.g., stretch) and pathophysiological (e.g., inflammation, edema) stimuli likely vary throughout these regions. Our data provide a neuroanatomical basis for understanding afferent responses in vivo .

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Section: Discussionmentioning

confidence: 99%

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Kim

Patil

Hadley

et al. 2022

eNeuro

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“…However, general anesthesia results in decreased conductivity of neural pathways and inhibition of the central nervous system. Our model did not allow us to investigate the cortical modulation of the cough reflex nor its behavioral component ( Plevkova et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of Inhaled Corticosteroids on the Modulation of Respiratory Defensive Reflexes During Artificial Limb Exercise in Ovalbumin-Sensitized Rabbits

et al. 2022

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IntroductionCough is a major lower airway defense mechanism that can be triggered by exercise in asthma patients. Studies on cough reflex in experimental animal models revealed a decrease of cough reflex sensitivity during exercise in healthy animals, but a lack of desensitization in ovalbumin-sensitized rabbits. The aim of our study is to evaluate the impact of inhaled corticosteroids on cough reflex during artificial limb exercise in an animal model of eosinophilic airway inflammation.Materials and MethodsSixteen adult ovalbumin-sensitized rabbits were randomly divided into two groups. The “OVA-Corticoid” group (n = 8) received inhaled corticosteroids (budesonide; 1 mg/day during 2 consecutive days) while the “OVA-Control” (n = 8) group was exposed to saline nebulization. The sensitivity of defensive reflexes induced by direct mechanical stimulation of the trachea was studied in anesthetized animals, at rest and during artificial limb exercise. Cell count was performed on bronchoalveolar lavage fluid and middle lobe tissue sections to assess the level of eosinophilic inflammation.ResultsAll rabbits were significantly sensitized but there was no difference in eosinophilic inflammation on bronchoalveolar lavage or tissue sections between the two groups. Artificial limb exercise resulted in a significant (p = 0.002) increase in minute ventilation by 30% (+ 209 mL.min–1, ± 102 mL/min–1), with no difference between the two groups. 322 mechanical tracheal stimulations were performed, 131 during exercise (40.7%) and 191 at rest (59.3%). Cough reflex was the main response encountered (46.9%), with a significant increase in cough reflex threshold during artificial limb exercise in the “OVA-Corticoid” group (p = 0.039). Cough reflex threshold remained unchanged in the “OVA-Control” group (p = 0.109).ConclusionInhaled corticosteroids are able to restore desensitization of the cough reflex during artificial limb exercise in an animal model of airway eosinophilic inflammation. Airway inflammation thus appears to be involved in the physiopathology of exercise-induced cough in this ovalbumin sensitized rabbit model. Inhaled anti-inflammatory treatments could have potential benefit for the management of exercise-induced cough in asthma patients.

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“…The present application describes a series of novel tetrazole derivatives as TRPA1 inhibitors for the treatment of idiopathic lung disease or cough. Further, the application discloses compounds, their preparation, use, and pharmaceutical composition, and treatment. …”

Section: Discussionmentioning

confidence: 99%

Tetrazole Derivatives as TRPA1 Inhibitors for Treating Idiopathic Lung Disease or Cough

Sabnis¹

2022

ACS Med. Chem. Lett.

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Transient receptor potential channels (TRP channels) are a group of voltage-gated ion channels located mostly on the plasma membrane of numerous mammalian cell types. There are approximately 30 TRP channels sorted into several groups: TRPA, TRPC, TRPM, TRPML, TRPN, TRPP, and TRPV. Transient receptor potential ankyrin 1 (TRPA1) is best known as a sensor for environmental irritants giving rise to somatosensory modalities such as pain, cold, and itch.TRPA1 is activated by a number of reactive, electrophilic stimuli and non-reactive compounds implicated in cough associated with asthma, chronic pulmonary obstructive disease (COPD), idiopathic pulmonary fibrosis (IPF), postviral cough, and chronic idiopathic cough. TRPA1 antagonists are effective in studies of atopic dermatitis, contact dermatitis, and psoriasis-associated itch.The present application describes a series of novel tetrazole derivatives as TRPA1 inhibitors for the treatment of idiopathic lung disease or cough. Further, the application discloses compounds, their preparation, use, and pharmaceutical composition, and treatment.Definitions. A = phenyl, thienophenyl, benzothiophenyl, and benzofuranyl, unsubstituted or substituted with one or more member of the group R 1 selected from CN, halogen,

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Animal models of cough

Cited by 13 publications

References 106 publications

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Impact of Inhaled Corticosteroids on the Modulation of Respiratory Defensive Reflexes During Artificial Limb Exercise in Ovalbumin-Sensitized Rabbits

Tetrazole Derivatives as TRPA1 Inhibitors for Treating Idiopathic Lung Disease or Cough

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