xRead - Nonallergic Rhinitis (September 2025)

Clinical Reviews in Allergy & Immunology (2024) 67:40–46

41

SP

Substance P

nasal blockage, and increased tear production. This is attributed to its ability to activate TRPV1 receptors, resulting in an influx of cations into nerve terminals and an increase in intracellular Ca 2+ concentration, which in turn stimulates the release of neu ropeptides and potentially triggers an inflammatory response. The therapeutic effect of intranasal capsaicin is believed to be due to the permanent degeneration of nerve terminals due to the overwhelming influx of Ca 2+4 . Recent clinical trials, employ ing more biochemical approaches, have further elucidated cap saicin’s mechanism. Treatment with capsaicin has been shown to reduce the expression of TRPV1, TRPM8, and PGP 9.5 in patients with idiopathic rhinitis. Importantly, capsaicin does not appear to alter mast cell marker c-KIT or nasal epithelial mor phology, nor does it induce apoptosis or necrosis in cultured human nasal epithelial cells and mast cells [3]. These findings suggest that capsaicin may offer a novel therapeutic approach for NAR, specifically targeting the TRPV1-SP nociceptive signal ing pathway without affecting mast cell function or nasal epi thelial integrity. Rhinitis, encompassing both allergic rhinitis (AR) and non-allergic rhinitis (NAR), is a prevalent condition glob ally, with a median global prevalence of 29.4%, 18.1%, and 12.0% respectively [4]. While geographic variations exist, studies consistently indicate a rising prevalence of rhinitis in recent decades [2]. The significant socio-economic impact of rhinitis, stemming from untreated or inadequately treated cases, includes absenteeism and presenteeism, leading to decreased productivity and increased healthcare costs [4]. Effective treatments and guideline-based care hold the potential for substantial cost savings. In recent years, clinical trials investigating capsaicin solu tions for NAR have shown promising results. However, despite a previous review with only four studies included [5], a com prehensive analysis and systematic review of the literature are still lacking, highlighting the need for evidence-based medicine methodologies and a sufficient number of published clinical tri als. The absence of approved mass-produced medications spe cifically for clinical application underscores the urgent need for a meta-analysis and systematic review to address these gaps and pave the way for effective treatment options for NAR. Methods This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement. In addition, this review has been registered on PROSPERO as CRD42023481563.

TNSS VAS OD PCR

T otal nasal symptom scores V isual analog scale

Optical density

P olymerase chain reaction PGP 9.5 P rotein gene product 9.5 TRE T rigeminal reflex test NGF N erve growth factor

Introduction Rhinitis, an inflammatory condition affecting the nasal pas sages, includes two distinct categories: allergic rhinitis (AR) and non-allergic rhinitis (NAR). While AR is readily diag nosed through IgE-mediated testing [1], the diagnosis of NAR, also known as idiopathic rhinitis (IR), relies on exclud ing other potential causes, thereby posing a significant diag nostic challenge. NAR is characterized by nasal symptoms such as congestion, sneezing, and postnasal drip, without an identifiable allergen or structural abnormality. Although the exact cause remains unclear, it is believed that heightened nasal mucosa reactivity is involved in the pathology, poten tially linked to dysregulation of the autonomic nervous system in response to non-immunological stimuli, such as variations in temperature, potent odors, and airborne irritants. This dif fers from AR, which is initiated by an immunoglobulin E (IgE)-mediated reaction [1]. Clinically, distinguishing AR and NAR requires a combination of specific IgE levels or skin prick tests and a comprehensive medical history [2]. However, managing NAR is significantly challenging. While intranasal antihistamines and corticosteroids offer temporary relief, their efficacy is limited and raises concerns regarding potential side effects, particularly in children and pregnant women. The per sistent nature of NAR symptoms and the limitations of current therapies have necessitated the exploration of novel treatment strategies. Capsaicin, known for its efficacy in managing other conditions including neuropathic pain, osteoarthritis, and obe sity, has emerged as a potential therapeutic option for NAR. Its mechanism of action, including activation of transient receptor potential vanilloid subfamily 1 (TRPV1), suggests the potential for addressing the heightened nasal reactivity associated with this condition. Clinical trials investigating capsaicin for NAR treatment are ongoing, offering hope for patients with this troubling condition by potentially a more effective and lasting solution. Capsaicin (C 18 H 27 NO 3 ), a naturally occurring alkaloid extracted from chili peppers, holds promise as a treatment for non-allergic rhinitis (NAR). As an agonist of the transient recep tor potential vanilloid subfamily 1 (TRPV1) receptor, capsaicin exerts its therapeutic effect by ablating the TRPV1-SP nocic eptive signaling pathway in the nasal mucosa [3]. Upon nasal application, capsaicin elicits burning sensations, nasal discharge,

Criteria for Considering Studies for this Review

This study included both randomized controlled trials and quasi-randomized controlled trials, acknowledging the