Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context
Summary: Background: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory ner...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396424000112 |
| _version_ | 1797350894912667648 |
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| author | Aung Aung Kywe Moe Nabita Singh Matthew Dimmock Katherine Cox Lorcan McGarvey Kian Fan Chung Alice E. McGovern Marcus McMahon Amanda L. Richards Michael J. Farrell Stuart B. Mazzone |
| author_facet | Aung Aung Kywe Moe Nabita Singh Matthew Dimmock Katherine Cox Lorcan McGarvey Kian Fan Chung Alice E. McGovern Marcus McMahon Amanda L. Richards Michael J. Farrell Stuart B. Mazzone |
| author_sort | Aung Aung Kywe Moe |
| collection | DOAJ |
| description | Summary: Background: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI). Methods: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation. Findings: Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls. Interpretation: Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs. Funding: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd. |
| first_indexed | 2024-03-08T12:52:36Z |
| format | Article |
| id | doaj.art-a6a911536d944da982fcd2ec5a60ae8c |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T12:52:36Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-a6a911536d944da982fcd2ec5a60ae8c2024-01-20T04:45:47ZengElsevierEBioMedicine2352-39642024-02-01100104976Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in contextAung Aung Kywe Moe0Nabita Singh1Matthew Dimmock2Katherine Cox3Lorcan McGarvey4Kian Fan Chung5Alice E. McGovern6Marcus McMahon7Amanda L. Richards8Michael J. Farrell9Stuart B. Mazzone10Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC, Australia; Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, AustraliaDepartment of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, AustraliaDepartment of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, Australia; School of Allied Health Professions, Keele University, Staffordshire, UKCentre for Human Psychopharmacology, Swinburne University, AustraliaWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UKExperimental Studies Unit, National Heart & Lung Institute, Imperial College London, UK; Department of Respiratory Medicine, Royal Brompton and Harefield Hospital, London, UKDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, AustraliaDepartment of Respiratory and Sleep Medicine, Austin Hospital, Heidelberg, AustraliaDepartment of Otolaryngology, The Royal Melbourne Hospital, Parkville, VIC, AustraliaDepartment of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, Australia; Monash Biomedical Imaging, Monash University, Clayton, VIC, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, Australia; Corresponding author.Summary: Background: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI). Methods: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation. Findings: Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls. Interpretation: Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs. Funding: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd.http://www.sciencedirect.com/science/article/pii/S2352396424000112Vagal sensoryCoughBrain imagingPurinergicBrainstemATP |
| spellingShingle | Aung Aung Kywe Moe Nabita Singh Matthew Dimmock Katherine Cox Lorcan McGarvey Kian Fan Chung Alice E. McGovern Marcus McMahon Amanda L. Richards Michael J. Farrell Stuart B. Mazzone Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context EBioMedicine Vagal sensory Cough Brain imaging Purinergic Brainstem ATP |
| title | Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context |
| title_full | Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context |
| title_fullStr | Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context |
| title_full_unstemmed | Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context |
| title_short | Brainstem processing of cough sensory inputs in chronic cough hypersensitivityResearch in context |
| title_sort | brainstem processing of cough sensory inputs in chronic cough hypersensitivityresearch in context |
| topic | Vagal sensory Cough Brain imaging Purinergic Brainstem ATP |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424000112 |
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