NMDA and GABA receptors as potential targets in cough hypersensitivity syndrome

Chung, Kian Fan

doi:10.1016/j.coph.2015.03.002

Cited by 31 publications

(14 citation statements)

References 101 publications

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“…The main adverse events associated with baclofen were somnolence, dizziness, and fatigue. 94 Although baclofen remains a potential area for development, 95 no conclusions can be drawn about its effectiveness until RCTs are available.…”

Section: Baclofenmentioning

confidence: 99%

Management of chronic refractory cough

Gibson

Vertigan

2015

BMJ

110

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Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.

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Section: Baclofenmentioning

confidence: 99%

Management of chronic refractory cough

Gibson

Vertigan

2015

BMJ

110

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“…RARs in the intrapulmonary airways very rarely evoke cough, but usually provoke other reflexes, such as hyperpnea/tachypnea, augmented breaths, bronchoconstriction and laryngeal closure. Cough-related afferents may also originate from bronchopulmonary C-fibers (Coleridge and Coleridge 1986;Widdicombe, 1998;Lee and Pisarri 2001;Canning et al, 2006bCanning et al, , 2014Mori 2010, 2011;Chung 2015). In anesthetized animals, C-fiber stimulation has consistently failed to evoke coughing.…”

Section: Cough-related Afferent Fibersmentioning

confidence: 99%

Brainstem mechanisms underlying the cough reflex and its regulation

Mutolo

2017

Respiratory Physiology & Neurobiology

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A B S T R A C TCough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced.

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“…GABAB receptor agonists have also been shown to possess antitussive effects in patients and in animals independent of their effects on transient lower esophageal sphincter relaxation (TLESR; the major cause of reflux) (15,16). Use of GABAB receptor agonists such as baclofen acting both in the central nervous system and peripheral tissues may represent novel therapeutic approaches (2,17). Baclofen also has been used in both experimental models (18) and in humans (19,20) with promising results.…”

Section: Gabab Receptor Antagonistmentioning

confidence: 99%

“…There has been some progress in the new therapeutic options of orally administered, specific neuromodulators for 'non-specific' antitussives (2). However, there is a paucity of well-controlled clinical studies documenting evidence for the use of many of the drug classes today.…”

mentioning

confidence: 99%