Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

Bessac, Bret F.; Jordt, Sven‐Eric

doi:10.1152/physiol.00026.2008

Cited by 344 publications

(362 citation statements)

References 136 publications

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Section: Resultsmentioning

confidence: 99%

“…From the TRP superfamily, the main triggers in the airways are the TRPV and the TRPA ion channels, expressed on the C-fibers of sensory nerves [27,113–115]. Nociceptive sensory neurons also take part in protective reflexes, including the cough and sneeze reflexes, and release inflammatory neuropeptides in the periphery upon stimulation by different environmental stimuli [113]. The TRPA1 receptor antagonist GRC17536 has shown a statistically significant and clinical response in a Phase IIa clinical trial for the treatment of diabetic peripheral neuropathy [116]; however, an unpublished placebo-controlled study of GRC17536 in CC did not reduce 24 h cough frequency, cough VAS, or citric acid cough reflex sensitivity [21].…”

Section: Resultsmentioning

confidence: 99%

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An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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“…and inhaled chemical irritants (e.g., acrolein, toluene diisocyanate, etc.) (7,25,41,46). Immunohistochemical studies have shown that TRPV1 channels are also colocalized with certain sensory neuropeptides, such as tachykinins and CGRP, in the sensory terminals (51).…”

Section: Discussionmentioning

confidence: 99%

Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-α in rat pulmonary sensory neurons

Gu²,

Lin³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hu Y, Gu Q, Lin RL, Kryscio R, Lee LY. Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-␣ in rat pulmonary sensory neurons. Am J Physiol Lung Cell Mol Physiol 299: L483-L492, 2010. First published July 16, 2010 doi:10.1152/ajplung.00111.2010.-TNF␣, a proinflammatory cytokine known to be involved in the pathogenesis of allergic asthma, has been shown to induce hyperalgesia in somatic tissue via a sensitizing effect on dorsal root ganglion neurons expressing transient receptor potential vanilloid type 1 receptor (TRPV1). Because TRPV1-expressing pulmonary sensory neurons play an important role in regulating airway function, this study was carried out to determine whether TNF␣ alters the sensitivity of these neurons to chemical activators. Responses of isolated nodose and jugular ganglion neurons innervating the rat lungs were determined by measuring the transient increase in intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i). Our results showed the following. 1) A pretreatment with TNF␣ (50 ng/ml) for ϳ24 h increased significantly the peak ⌬[Ca 2ϩ ]i evoked by capsaicin (Cap) in these neurons. A pretreatment with the same concentration of TNF␣ for a longer duration (ϳ48 h) did not further increase the response, but pretreatment for a shorter duration (1 h) or with a lower concentration (25 ng/ml, 24 h) failed to enhance the Cap sensitivity.2) The same TNF␣ pretreatment also induced similar but less pronounced and less uniform increases in the responses to acid (pH 6.5-5.5), 2-aminoethoxydiphenyl borate (2-APB), a common activator of TRPV1, V2, and V3 channels, and allyl isothiocyanate (AITC), a selective activator of TRPA1 channel. 3) In sharp contrast, the responses to ATP, ACh, and KCl were not affected by TNF␣. 4) The TNF␣-induced hypersensitivity to Cap was not prevented by pretreatment with indomethacin (30 M). 5) The immunoreactivity to both TNF receptor types 1 and 2 were detected in rat vagal pulmonary sensory neurons. In conclusion, prolonged treatment with TNF␣ induces a pronounced potentiating effect on the responses of isolated pulmonary sensory neurons to TRPV1 activators. This action of TNF␣ may contribute in part to the airway hyperresponsiveness induced by this cytokine. intracellular calcium; pulmonary afferent; transient receptor potential vanilloid type 1; airway inflammation; asthma AN IMPORTANT ROLE OF TNF␣ in the pathogenesis of allergic asthma has been extensively documented (6,9,28,47). TNF␣ can be released from a variety of cell types in the airways, particularly macrophages, monocytes, and mast cells. TNF␣, either newly synthesized or preformed and stored constitutively within the mast cell granules, is coreleased with other potent mediators such as histamine and tryptase via the IgE-dependent mechanism (9, 21, 47). TNF␣ was detected in bronchoalveolar lavage fluid, sputum, exhaled breath condensate, and serum of asthmatic patients during asthmatic attack or following antigen inhalation challenge (12,33,39). Furthermore, it has been shown that TNF␣ is releas...

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“…Members of the transient receptor potential (TRP) superfamily of ion channels play a key role in the response of sensory neurons to inflammatory mediators and noxious chemical stimuli, initiating respiratory depression, cough, glandular secretions and other protective responses [10]. Jordt et al recently suggested that TRPA1 may function as an integrator of chemical and immunological stimuli modulating inflammation in the airways [10].…”

mentioning

confidence: 99%

“…Jordt et al recently suggested that TRPA1 may function as an integrator of chemical and immunological stimuli modulating inflammation in the airways [10]. Furthermore, chemical irritant-induced activation of TRPA1 may trigger the release of neuropeptides and chemokines in the airways, thereby exacerbating the cellular and tissue inflammatory response observed in allergic individuals [11].…”

mentioning

confidence: 99%

Exercise-induced asthma: why is it so frequent in Olympic athletes?

Moreira¹,

Delgado

Carlsen

2011

Expert Review of Respiratory Medicine

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Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

Cited by 344 publications

References 136 publications

An update and systematic review on drug therapies for the treatment of refractory chronic cough

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-α in rat pulmonary sensory neurons

Exercise-induced asthma: why is it so frequent in Olympic athletes?

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