Workshop: Tuning the ‘cough center’

Widdicombe, J. G.; Tatár, M.; Fontana, Giovanni; Hanácek, J; Davenport, Paul W.; Lavorini, Federico; Bolser, Donald C.

doi:10.1016/j.pupt.2010.12.010

Cited by 18 publications

(8 citation statements)

References 96 publications

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“…Moreover, the exact mechanism underlying our findings may involve the cough center. At the level of the brainstem, the nucleus tractus solitarius associated with the cough center is not only regulated by the higher cortical center; it is also closely related to other functional centers of the body ( Widdicombe et al, 2011 ). The paraventricular nucleus, a center for regulating body temperature, receives afferent terminations from the nucleus tractus solitarius, emits efferent projections to the cough center, and transmits synaptic signals through SP and its receptor, neurokinin 1 ( El-Hashim et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

et al. 2020

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Cough exacerbation in cold environments is a characteristic feature of patients with chronic cough. There is consensus that inhalation of cold air stimulates cough receptors but this idea is not consistent with the fact that cold air is usually unable to directly enter the lower airway. To elucidate the effects of cold environments and transient receptor potential ankyrin 1 (TRPA1) on cough, we compared cough reactivity, airway inflammation, and TRPA1 expression in guinea pigs with chronic cough induced by the repeated inhalation of citric acid for 15 days. The guinea pigs were exposed to cold environments for three consecutive days from day 13 to 15. Repeated inhalation of citric acid increased cough reactivity to inhaled cinnamaldehyde. We found that exposure to cold environments further aggravated cough hyperreactivity in guinea pigs with chronic cough, but not in normal guinea pigs. Cough hyperreactivity was promoted when the whole body and trunk-limbs, but not the heads, of the guinea pigs were exposed to cold environments, and abolished by pretreating the skin through immersion in the TRPA1 antagonist, HC-030031. Substance P levels in bronchoalveolar lavage fluid, and TRPA1 expression in the trachea and skin, were increased in guinea pigs when the whole body and trunk-limbs, rather than the head, were exposed to cold environments. However, this trend was also abolished by pretreatment of the skin via immersion in HC-030031. Similar changes in TRPA1 expression were also detected in the sensory fibers of the trachea and skin, as identified by immunofluorescence and laser-scanning confocal microscopy analysis. These results suggest that exaggerated cough hyperreactivity induced by cold environments may be related to activation of the cold-sensing TRPA1 signaling pathway in the skin, rather than the inhalation of cold air.

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Section: Discussionmentioning

confidence: 99%

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

et al. 2020

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“…In addition to these primary cough pathways, cough can be sensitized by additional sensory neuron inputs, such as from the nose, ear, or esophagus, explaining why rhinitis, excessive earwax, and gastroesophageal reflux can all be associated with excessive coughing. 20 In the clinical setting the challenge with treating cough and CHS is in understanding the underlying cause. This is complicated by the heterogeneous neural process described above but additionally confounded by the diversity of pathologies associated with the 100 or so disorders that are accompanied by excessive cough.…”

Section: Substance Pmentioning

confidence: 99%

Translational review: Neuroimmune mechanisms in cough and emerging therapeutic targets

McGovern

Short

Moe

et al. 2018

Journal of Allergy and Clinical Immunology

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Cough is an essential defensive behavior for maintaining airway patency and to protect the lungs from potentially harmful agents. However, inflammatory pathologies can sensitize and activate the neural pathways regulating cough, leading to excessive and nonproductive coughing that serves little protective utility. Problematic cough continues to be one of the most common reasons for seeking medical advice, yet for many patients, it can be refractory to disease-specific treatments and currently available antitussive therapies. The effect of inflammation on cough neural processing occurs not only at the level of the bronchopulmonary sensory nerve terminals but also within the nervous system at multiple peripheral and central sites. Sensory nerves also actively regulate inflammation, and it is therefore a complex interplay between the immune and nervous systems that contributes to chronic cough and the associated sensory hypersensitivities. In this review we provide a brief overview of cough neurobiology in health and disease and then explore the peripheral and central nervous system sites at which neuroimmune interactions can occur. We present advancements in the development of effective antitussive therapies and suggest novel targets for future consideration.

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“…After glottal closure and rapid compression of the enlarged lung volume via the so-called Hering-Breuer expirium facilitating reflex (HBEFR) provokes strong expiratory effort (Marek et al, 2008), manifesting during the expulsive phase of CR. In addition to the HBIR and HBEFR, the proprioceptive reflexes of the respiratory muscles and stimulation of RARs, SARs, A δ , and C-fibers in the airways and lungs in non-paralyzed subjects, can also contribute to the modification of cough efforts (Korpas and Tomori, 1979; Widdicombe, 2006, 2011; Widdicombe et al, 2011a,b). Studies in guinea pigs suggest that a previously unrecognized subtype of airways afferent nerve—cough receptors—play the primary role in regulating this defensive reflex.…”

Section: Reflex Modifications Of Breathingmentioning

confidence: 99%

Reversal of functional disorders by aspiration, expiration, and cough reflexes and their voluntary counterparts

Tomori¹,

Donič²,

Benacka³

et al. 2012

Front. Physio.

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Agonal gasping provoked by asphyxia can save ~15% of mammals even from untreated ventricular fibrillation (VF), but it fails to revive infants with sudden infant death syndrome (SIDS). Our systematic study of airway reflexes in cats and other animals indicated that in addition to cough, there are two distinct airway reflexes that may contribute to auto-resuscitation. Gasp- and sniff-like spasmodic inspirations (SIs) can be elicited by nasopharyngeal stimulation, strongly activating the brainstem generator for inspiration, which is also involved in the control of gasping. This “aspiration reflex” (AspR) is characterized by SI without subsequent active expiration and can be elicited during agonal gasping, caused by brainstem trans-sections in cats. Stimulation of the larynx can activate the generator for expiration to evoke the expiration reflex (ExpR), manifesting with prompt expiration without preceding inspiration. Stimulation of the oropharynx and lower airways provokes the cough reflex (CR) which results from activating of both generators. The powerful potential of the AspR resembling auto-resuscitation by gasping can influence the control mechanisms of vital functions, mediating reversal of various functional disorders. The AspR in cats interrupted hypoxic apnea, laryngo- and bronchospasm, apneusis and even transient asphyxic coma, and can normalize various hypo- and hyper-functional disorders. Introduction of a nasogastric catheter evoked similar SIs in premature infants and interrupted hiccough attacks in adults. Coughing on demand can prevent anaphylactic shock and resuscitate the pertinent subject. Sniff representing nasal inspiratory pressure and maximal inspiratory and expiratory pressures (MIP and MEP) are voluntary counterparts of airway reflexes, and are useful for diagnosis and therapy of various cardio-respiratory and neuromuscular disorders.

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Workshop: Tuning the ‘cough center’

Cited by 18 publications

References 96 publications

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

Translational review: Neuroimmune mechanisms in cough and emerging therapeutic targets

Reversal of functional disorders by aspiration, expiration, and cough reflexes and their voluntary counterparts

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