TRPV1 inhibition does not prevent cold dry air-elicited symptoms in non-allergic rhinitis

Murdoch, Robert; Bareille, Philippe; Denyer, Jane; Newlands, Amy; Bentley, Johanne; Smart, Kevin; Yarnall, Katy; Patel, Deepen

doi:10.5414/cp202013

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…The TRPV1 antagonist SB-705498 revealed no negative properties but a somewhat surprising effect only on the capsaicin cough sensitivity, not on the cough symptoms [ 65 ]. However, this is in concordance with other reports studying rhinitis and pruritus [ 100 , 101 , 102 , 103 ] showing no improvement from treatment with SB-705498. The results could suggest that TRPV1 may not be of such great importance in chronic cough as earlier believed, but the evident relation between chronic cough, TRPV1 expression and cough sensitivity to inhaled capsaicin contradicts such a paradigm change.…”

Section: Discussionsupporting

confidence: 93%

TRPV1 and TRPM8 in Treatment of Chronic Cough

Millqvist

2016

Pharmaceuticals

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Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician’s awareness. The possibilities of modulating airway transient receptor potential (TRP) ion channels may indicate new ways to treat the persistent cough “without a reason”. The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction.

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Section: Discussionsupporting

confidence: 93%

TRPV1 and TRPM8 in Treatment of Chronic Cough

Millqvist

2016

Pharmaceuticals

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“…Although some studies have previously examined the overexpression of TRPV1 in nasal airway inflammation [ 5 ], clinical trials have failed to demonstrate any clinical efficacy of the topical inhibition of TRPV1 [ 9 - 11 ]. It has been suggested that the reason underlying this lack of efficacy may be that neuronal TRPV1 was focused in human airway inflammation, rather than other cell types [ 6 , 20 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that TRPV1 was up-regulated in rhinitis, there has been little translation to clinical efficacy. In double-blinded randomized cross-over studies, the topical intranasal TRPV1 antagonist, SB-705498 did not alleviate allergen-induced or cold dry air-elicited symptoms in allergic or non-allergic rhinitis [ 9 - 13 ]. This mismatch between the over-expression of TRPV1 in nasal mucosa and the lack of clinical efficacy of TRPV1 antagonist treatment draws our attention to a possible alternative target cell type, immune cells.…”

Section: Introductionmentioning

confidence: 99%

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis

et al. 2015

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Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.

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“…TRPV1 was considered a prime target for neurogenic rhinitis therapy, but a recent study proved negative when cold dry air challenges were used, 292 but antagonism did reduce the response to capsaicin. 293 …”

Section: Montelukastmentioning

confidence: 99%

BSACI guideline for the diagnosis and management of allergic and non‐allergic rhinitis (Revised Edition 2017; First edition 2007)

Scadding

Kariyawasam

Scadding

et al. 2017

Clin Experimental Allergy

235

238

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This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

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TRPV1 inhibition does not prevent cold dry air-elicited symptoms in non-allergic rhinitis

Abstract: SB-705498 12 mg for 14 days did not alleviate the CDA-induced symptoms of NAR. Despite engagement of the TRPV1 receptor, there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.

Cited by 14 publications

References 31 publications

TRPV1 and TRPM8 in Treatment of Chronic Cough

TRPV1 and TRPM8 in Treatment of Chronic Cough

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis

BSACI guideline for the diagnosis and management of allergic and non‐allergic rhinitis (Revised Edition 2017; First edition 2007)

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