The Neurophysiology and Pharmacology of the Cough Reflex
Lead Research Organisation:
University of Manchester
Department Name: Medical and Human Sciences
Abstract
Cough is the most common symptom for which patients seek medical advice and it is estimated that cough costs the UK economy £1 billion each year. Despite this we know very little about the processes which lead to coughing and we do not have effective treatments for cough. Patients with chronic cough describe themselves as very sensitive to smoky atmospheres and temperature changes and even talking and laughing can trigger coughing. Much more is known about the pain pathways and how they become too sensitive, causing chronic pain. This programme of work draws on this knowledge to better understand how the nerves involved in the cough reflex can become over sensitive. New techniques will be developed for testing new treatments for this very common and troublesome symptom.
Technical Summary
Cough is the most common symptom for which patients seek medical advice. It is estimated that cough costs the UK economy £1 billion each year. Chronic cough affects 14-23% of the non-smoking population and has a substantial impact on quality of life.
Patients with chronic cough have cough reflex hypersensitivity. This has been considered to be due to associated conditions such as such as asthma, reflux and nasal disease, but disease specific treatments are relatively ineffective. Cough reflex hypersensitivity may be analogous to pain hypersensitivity i.e. due to neuroplastic processes. This has been extensively studied in pain and the phenomena of peripheral and central sensitisation described. The aim of this programme of work is to extend these principles into the study of cough reflex hypersensitivity.
Peripheral sensitisation will be studied by assessing the cough responses to a range of peripheral nerve sensitizers and using specific blocking agents e.g. TRPV1 antagonists, in patients with cough due to asthma, reflux disease, nasal disease and chronic obstructive airway disease.
Central sensitisation will be investigated by inducing cough reflex sensitivity in healthy volunteers using oesophageal acid stimulation. The neuropharmacological basis of this process will be studied with NMDA receptor antagonism. In similar studies, the role of central sensitisation in patients with chronic cough will be established, and confirmed by assessing the efficacy of novel treatments.
The interactions between peripheral and central sensitisation will also be studied, since the mechanical damage from coughing may be important in maintaining cough reflex hypersensitivity.
Currently anti-tussive therapies are relatively ineffective. This study will provide a new model for developing and testing effective anti-tussive therapies, for which there is a large unmet need.
Patients with chronic cough have cough reflex hypersensitivity. This has been considered to be due to associated conditions such as such as asthma, reflux and nasal disease, but disease specific treatments are relatively ineffective. Cough reflex hypersensitivity may be analogous to pain hypersensitivity i.e. due to neuroplastic processes. This has been extensively studied in pain and the phenomena of peripheral and central sensitisation described. The aim of this programme of work is to extend these principles into the study of cough reflex hypersensitivity.
Peripheral sensitisation will be studied by assessing the cough responses to a range of peripheral nerve sensitizers and using specific blocking agents e.g. TRPV1 antagonists, in patients with cough due to asthma, reflux disease, nasal disease and chronic obstructive airway disease.
Central sensitisation will be investigated by inducing cough reflex sensitivity in healthy volunteers using oesophageal acid stimulation. The neuropharmacological basis of this process will be studied with NMDA receptor antagonism. In similar studies, the role of central sensitisation in patients with chronic cough will be established, and confirmed by assessing the efficacy of novel treatments.
The interactions between peripheral and central sensitisation will also be studied, since the mechanical damage from coughing may be important in maintaining cough reflex hypersensitivity.
Currently anti-tussive therapies are relatively ineffective. This study will provide a new model for developing and testing effective anti-tussive therapies, for which there is a large unmet need.
