Article

Capsaicin significantly reduces sinonasal polyps

Authors:
  • Clinics Medikol Zagreb, Croatia
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Abstract

Some reports indicate that topical nasal treatment with capsaicin, which is usually effective in reducing symptoms of vasomotor rhinitis, may also reduce symptoms in patients with nasal polyps. The aim of this study was to investigate the effect of topical capsaicin treatment in severe sinonasal polyposis. Nine non-allergic, non-asthmatic patients with diffuse eosinophilic nasal polyposis were subjected to topical capsaicin treatment: for 3 consecutive days 0.5 ml 30 micromol/l capsaicin solution and on days 4 and 5 100 micromol/l capsaicin solution was sprayed into each nostril. Coronary computed tomography (CT) images were made shortly before treatment. Baseline nasal lavages and a questionnaire containing subjective symptoms and nasal endosocpy were taken just prior to the first application. Nasal lavages were performed prior to and after the last treatment and over 4 weeks, endoscopy and subjective scores at each weekly visit, and correspondent CT scans 4 weeks after the treatment. CT images were analysed by computer, calculating the nose sinuses air volume (NSAV) from the surface of aerated parts of nasal and sinus cavities for each slice per patient prior to and after treatment. Statistical analysis was performed comparing NSAV, subjective scores, endoscopy scores and eosinophil cationic protein (ECP) levels in nasal lavages prior to and after treatment. Topical treatment with capsaicin significantly increased NSAV and very significantly improved subjective and endoscopy scores, but did not significantly alter ECP levels in nasal lavages.

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... The potent TRPV1 agonist capsaicin (the pungent principle in hot pepper) selectively excites and, in repeated high dosis, desensitizes or even reversibly damages a subpopulation of sensory nerve fiber terminals (13) . Capsaicin desensitization/denervation has been demonstrated to improve nasal symptoms in non-allergic rhinitis and CRS (11,(14)(15)(16)(17)(18)(19)(20) . ...
... Intranasal capsaicin desensitization or denervation can act only on neuronal terminals. It cannot reduce the number of mast cells (20) and can alleviate only certain forms of rhinitis and rhinosinusitis (11,(14)(15)(16)(17)(18)(19)(20) . There are data on capsaicin desensitization reducing symptoms in CRSwNP (35) but not in allergic rhinitis (11) possibly due to lack of impact on non-neuronal (i.e. ...
Article
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Background: Chronic rhinosinusitis (CRS) is a multifactorial upper airway disease with unclear etiology. Neuronal Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels have been implicated in the pathogenesis of CRS. We aimed to detect the expression of extraneuronal TRPV1 and TRPA1 receptors in nasal polyp (NP) tissue samples. Methodology: Samples were obtained from fourty-two CRS pateints with nasal polyp and sixteen healthy controls to measure receptor gene expression by quantitative PCR, protein localization by immunohistochemistry and cytokine profile by multiplex bead immunoassay. Results: Non-neuronal TRPV1, TRPA1 receptors were expressed in biopsy samples of NP. A population of mast cells and macrophages were immunopositive for TRPV1 and TRPA1. A fraction of plasma cells expressed TRPV1 but not TRPA1 and neither receptor was present on eosinophils. The local gene expression of extraneuronal TRPV1, TRPA1 receptors was also proven. TRPV1 mRNA levels were significantly increased in CRSwNP patients with asthma and allergic rhinitis compared to their NP counterparts. Conclusions: Elevated TRPV1 levels in comorbid asthma and allergy may have a function in CRSwNP. Subpopulation-specific TRPV1 presence on plasma and mast cells can indicate delicate roles in regulating activation and release of inflammatory mediators.
... In the forthcoming era of biological treatments for uncontrolled CRS, imaging may be viewed as an outcome measure of objective improvement rate. CT has been employed as an outcome measure following medical treatment in several studies regarding oral and topical glucocorticoids, amphotericin, and capsaicin B [51]. To increase the sensitivity of the mucosal response, some studies measured mucosal thickness or nasal/sinus air volume before and after therapy. ...
Article
Purpose of review Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of the sinonasal cavities classified into two major phenotypes: CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The diagnosis of CRS is based on clinical symptoms associated with imaging and/or nasal endoscopy findings of mucosal inflammation. Recent findings Recently, novel biological therapies have emerged as therapeutic options for CRSwNP. Imaging is helpful in deciding whether surgery is likely to be beneficial and in guiding surgery. It can also help demonstrate a clinical response to medical therapy. However, specific guidelines concerning the role of imaging in CRwNP are lacking. Summary This article provides a comprehensive and critical multidisciplinary review of the role of conventional radiology, computed tomography (CT), and magnetic resonance imaging (MRI) in the diagnosis and characterization of CRSwNP. Since the complete characterization of nasal polyps on CT or MR images is very challenging, we provide a critical review of the best imaging methods and essential reporting elements used to assess nasal polyps.
... So far, CT was used as an outcome measure after medical treatment in several studies regarding oral and topical steroids, amphotericin B, capsaicin. 50 To increase sensitivity of mucosal response some of the studies used mucosal thickness or nasal/sinus air volume before and after the treatment. Objective improvement after biological treatment (omalizumab, mepolizumab, dupilumab) for CRS was also evaluated using Lund-Mackay score before and 8-24 weeks after the treatment. ...
Article
Background Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. Purpose The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. Material and Methods This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, „severity staging“, „diagnostic accuracy “and „imaging “resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. Results CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. Conclusions MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.
... Baudoin et al. investigated the effects of topical treatment with capsaicin in nine patients who had become unresponsive to local steroid therapy and refused systemic steroids or surgical polypectomy [105]. Capsaicin was sprayed in each nostril once a day for five days; 4.5 µg were given in the first three days, followed by 15 µg in the last two days. ...
Article
Background: Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the substance responsible of the irritation caused by the contact of chili peppers with the skin or mucous membranes. This protoalkaloid acts by stimulating the transient receptor potential cation channel subfamily V member 1 (TRPV1), which is mainly expressed by nociceptive fibers of peripheral sensory neurons, but is also present in the central nervous system, and in some non-neuronal cells. Following the initial, intense neuronal excitation, a brief refractory period occurs. However, repeated and massive exposures to capsaicin can impair nociceptive fiber function for weeks or months. During this lapse of time, disorders related to the hyperreactivity of peripheral nociceptors are abolished or greatly reduced. Capsaicin has been utilized to treat several diseases of upper airways. Objective: The objective of this review was to report the latest findings on the use of Capsaicin in the treatment of upper airway diseases. Results: Capsaicin effectiveness has been proved in non allergic rhinitis. Some studies suggest that this substance may be also effective in nasal polyposis and in the burning mouth syndrome. No clear evidence has been obtained about its use in allergic rhinitis. Conclusion: To date, the use of capsaicin to treat upper airway diseases is still limited in clinical practice. This may originate by the lack of strong, conclusive evidences of its effectiveness, by the variety of therapeutic schemes used in literature, and finally by the unpleasant effects of the exposure to capsaicin, which are only partly relieved by the pretreatment with local anesthetics.
... These lesions are often quite impossible to distinguish clinically and are labelled as nasal polyp. [7] Histopathological examination of such polypoidal masses show a spectrum of lesions ranging from nonneoplastic ones to neoplastic tumors including benign and malignant neoplasms. [8] The true nasal polyps are the tumor like nonneoplastic polypoidal masses arising from nasal cavity and sinuses. ...
Article
Background: Nasal Polyp is commonly encountered in clinical practice and important from clinical and pathological perspectives as they have varieties of histological patterns. The Polypoidal masses in nasal cavity form a complex group of lesions with wide spectrum of histopathological features, mainly grouped under allergic and inflammatory. Histopathological examination shows a spectrum of lesions ranging from the non-neoplastic ones to neoplastic tumors. Methods: Present study included 153 polypoidal lesions of the nasal cavity during a period of one year. All the tissues were fixed in 10% buffered formalin, processed, stained with H & E and studied for various histopathological patterns. Periodic acid Schiff’s and reticulin stains were used wherever necessary. Results: classifying the sinonasal lesions according to histo-pathological features into various types helps us to know the clinical presentation, treatment, clinical outcome and prognosis of the disease. Although most of nasal polyps sent for histopathology are inflammatory, secondary to infection or allergy, various benign and malignant lesions of nose may present as polypoidal masses, Conclusion: The study recommends, all polyps need histo-pathological examination. DOI: 10.21276/APALM.1173
... Furthermore, capsaicin did not alter levels of CD1 + , CD25 + , CD3 + , CD68 + , BMK13 + , IgE + , tryptase + , and chymase + cells in pan-neurogenic staining of nasal mucosa of NAR patients compared to controls (Blom et al. 1998). These findings imply that NAR does not involve alterations in a number of immunocompetent cells or modulation of neural tissue density and indicate that capsaicin's effectiveness in treating either NAR, MR, or AR may be attributable to a mechanism(s) unrelated to traditional AR inflammatory pathways (Baudoin et al. 2000). ...
Article
Full-text available
Capsaicin is a selective transient receptor potential vanilloid 1 (TRPV1) ion channel agonist and has been demonstrated to reduce nerve conduction of nociceptive C fibers in the trigeminal nerve without affecting conduction in Adelta fibers. This chapter reviews the classification of chronic rhinitis subtypes, the prevalence and epidemiology of nonallergic rhinitis (NAR), postulated pathophysiology and mechanisms of NAR including the role of transient receptor potential (TRP) ion channels and discusses the potential therapeutic benefits of capsaicin in the treatment of chronic rhinitis subtypes, specifically NAR. Evidence supports that hypersensitivity of TRP ion channels on sensory afferent neurons innervating nasal mucosa is responsible for inducing NAR symptoms. These symptoms, characterized as excessive nasal glandular secretion, nasal congestion, and headache, are mediated through neuropeptide release during axonal and parasympathetic reflexes which are initiated by a spectrum of nonspecific irritants that activate TRP channels. Rational approaches to treat the pathophysiology of NAR would be to develop therapies with selective TRPV1 agonist activity like capsaicin that target desensitization of TRP ion channels on sensory afferent nerves.
... Leukotriene receptor antagonists have recently been shown to be effective (Kieff et al 2005), but larger scale trials are required to prove their effi cacy. Topical capsaicin has also been shown to be effective, but side-effects including burning of the nasal mucosa limit its acceptability to patients (Baudoin et al 2000). There is little evidence to advocate the usage of other treatments including frusemide and interferon-alpha2a and neither of these is available in routine medical practice (Bateman et al 2003). ...
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Neural mechanisms contribute to many nasal symptoms and syndromes. Sensory nerve stimulation by irritants, mast cell products, and inflammatory mediators leads to sneezing and other systemic reflexes. Parasympathetic reflexes and sensory axon responses combine to increase nasal blood flow, fill venous sinusoids (which thickens the mucosa and reduces nasal patency), induce plasma extravasation, and stimulate glandular secretion of mucous and serous cell products. These putative roles for nerves and neuropeptides in pathologic events open new therapeutic avenues. Anticholinergic agents, peptide neurotransmitter agonists and antagonists, drugs to reduce or modulate sensory or parasympathetic nerve function, potent topically applied glucocorticosteroids, and agents to inactivate inflammatory, secretory, or vascular cells may be of use. Ablation of sensory nerves by topical application of the chili pepper neurotoxin capsaicin has been successful in reducing the symptoms of refractory vasomotor rhinitis.
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A radioimmunoassay was developed allowing measurement of the cytotoxic cationic ECP. The assay, which has a total incubation time of 3.5 hr, is a double antibody assay with radiolabelled ECP, covering the concentration range of 2-200 micrograms/l. Performance data show a detection limit of less than 2 micrograms/l and a cross-reactivity with eosinophil protein X (EPX/EDN) of less than 0.06%. The coefficient of variation (%) within the measuring range was, within assay 4.8-10.4, and total 6.6-12.0. The assay is useful for measurement in various body fluids including serum, nasal secretions and bronchoalveolar lavage fluid, and dilution of samples prior to analysis was generally not required. Sera from 100 apparently healthy individuals revealed a geometric mean of 6.0 micrograms ECP/l and a range (95%) of 2.3-15.9 micrograms/l. The elimination rate of ECP, t1/2, in vivo was estimated to be 65 min when ECP was measured in serum. Comparisons between this assay and a method previously described showed that the new method is superior with regard to precision and assay procedure.
Article
Nasal polyposis can be defined as a chronic inflammatory disease of the paranasal sinus mucosa, leading to a protrusion of benign edematous polyps from the meatus into the nasal cavities. Nasal polyps are histologically characterized by massive edema and accumulation of eosinophils. IgE-mediated allergy seems to play only a minor role in eosinophil accumulation, leaving the place for a new concept of non-allergic rhinitis with eosinophilia. The central question still remains, however, why eosinophils accumulate into nasal polyposis tissue. Some initial data show that tissue structural cells, i.e. epithelial cells or fibroblasts, could produce cytokines (GM-CSF) and play a role in eosinophil accumulation (micro-environmental theory). However, further studies showed, that GM-CSF was mainly produced by eosinophils themselves (autocrine theory), leading to the hypothesis of an intrinsic eosinophilic inflammatory process. Eosinophils may contribute to nasal polyp formation and growth not only through inflammation but also by exerting their effects on extracellular matrix including stimulation of collagen synthesis. Another feature associated with nasal polyposis is aspirin sensitivity. Some preliminary data indicate that eosinophils could also be involved in aspirin-sensitivity mechanisms.
Article
The presence of neuropeptide-containing sensory, parasympathetic and sympathetic nerves in human nasal mucosa is well established. However, information regarding the neuropeptide distribution in nasal polyps is still lacking. The aim of this study was to compare immunohistologically the presence and distribution of substance P (SP), vasoactive intestinal peptide (VIP) and bombesin-flanking peptide (BFP) in normal nasal mucosa and nasal polyps. The expression was studied using Formalin-fixed and paraffin-embedded biopsy sections from 20 patients with nasal polyps and 10 controls with normal nasal mucosa from the anterior part of the inferior turbinate. Indirect immunohistochemistry (APAAP method) with mono- and polyclonal antibodies was used. None of the control group but 5 patients of the nasal polyp group had an atopic disease. Comparing localization and intensity of the immunohistological reaction in nasal mucosa and nasal polyp tissue, there was no difference in the expression of the three neuroendocrine substances. There was no difference of expression in the polyposis group itself concerning allergic and nonallergic subjects. The results indicate that VIP, SP and BFP have an equal distribution in nasal polyps and normal nasal mucosa.
Article
The inflammatory process triggered by the nasal hyperreactivity, whether specific or aspecific, presents three components: immunomediation-neurogenic-interconnection between the nervous and the immunitary systems. Neuropeptides (eg SP and CGRP) are among the agents responsible for neurogenic phlogosis and, in our opinion, they contribute towards the onset of polyps. Capsaicin, which acts on the C fibres, has been applied locally (30 microns) by the AA in 15 patients affected by aspecific nasal hyperreactivity with polyps, in the course of a double blind study with an equal number of patients. Treatment was given once a week for 5 consecutive weeks in order to evaluate the effect on both the hyperreactivity and the polyps. Before and after each session and at the 1- and 3-month controls the following tests were carried out: assessment of symptoms, nasal endoscopy, sizing of the polyps, aspecific nasal provocation test and nasal cytology. Apart from an improvement in symptoms and in nasal hyperreactivity, results showed a reduction in the size of the polyps even though accompanied by a gradual increase of eosinophiles which was not correlated to a degranulation process.
Article
Nowadays nasal polyposis must be still considered an unsolved problem as the surgical procedures are unable to treat this pathology and the recurrence is very common. For this reason several Authors starting from the pathogenesis and the histological features have chosen a medical point of view at the aim of preventing the natural course of this disease. The present study experimented the effect of the furosemide locally administered in the prevention of polyps relapsing in subjects previously operated on. The Authors pointed out that the furosemide was able to decrease the nasal reactivity to the challenge with ultrasonic nebulized distilled water. Besides this drug locally administered for 3 months (once a day) maintained the nasal mucosa of the patients affected with hyperreactivity in a good functional condition without nasal obstruction. In fact no polyps were found at the objective examinations performed during the three years follow up and the values of acoustic rhinometry measurements were within the normal range. Finally the present research gave the opportunity to hypothesize the role of sodium, potassium and calcium ions transport regulated by drugs or other physiopathological events, in the physiology of the nasal mucosa.
Article
Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non-allergic non-infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa. We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment. There was a significant and long-term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals. As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.
Article
Capsaicin has been shown previously to reduce nasal complaints in patients with a non-allergic non-infectious perennial rhinitis. Proposed pathophysiological mechanisms for non-allergic non-infectious perennial rhinitis include a chronic inflammatory disorder of an antigenic or neurogenic nature as well as the possibility of a functional neuronal disorder. We hypothesized that the beneficial effect of capsaicin might be the result of a down-regulation of inflammation (by a reduction of inflammatory cells) or through modulation of neural tissue density. Patients were treated with either a placebo or capsaicin spray solution delivering 0.15 mg of capsaicin per nostril once every second or third day for a total of seven treatments. Both sides were treated each visit. Biopsies were taken before and 2 weeks, 3 months and 9 months after the treatment period. Immunohistochemical staining of the biopsy specimen was performed to ascertain the effect of treatment on immunocompetent cell densities (quantitative) and neural tissue densities (semi-quantitative) in the nasal mucosa. Nasal complaints were significantly reduced in the capsaicin-treated group. The number of CD1+, CD25+, CD3+, CD68+, BMK13+, IgE+, tryptase+, and chymase+ cells did not significantly differ between capsaicin and placebo group. No significant differences between both groups were found in pan-neurogenic staining of nasal mucosa using neurofilament and synaptophysine. Capsaicin aqueous nasal spray has previously been shown to reduce nasal complaints without affecting cellular homeostasis or overall neurogenic staining up to 9 months after treatment. Immunocompetent cells are not involved in non-allergic non-infectious perennial rhinitis.