Human TRPM8 peptide

Background: The therapeutic action of capsaicin treatment in patients with idiopathic rhinitis (IR) is based on ablation of the transient receptor potential cation channel subfamily V, receptor 1 (TRPV1)-substance P nociceptive signaling pathway. However, the functional consequences of capsaicin treatment on nasal nerve activation and the association between the reduction in nasal hyperreactivity (NHR) and response to capsaicin treatment remain unknown. Objective: We sought to study the effects of capsaicin nasal spray on the afferent innervation of the nasal mucosa by monitoring trigeminal nerve activity in patients with IR and healthy control (HC) subjects. Methods: A double-blind, placebo-controlled randomized trial with capsaicin nasal spray was performed involving 33 patients with IR and 12 HC subjects. Before and at 4, 12, and 26 weeks after treatment, nasal mucosal potentials (NMPs) were measured while exposing the nasal mucosa of patients with IR and HC subjects to aerosols with increasing doses of the chemical irritants allyl isothiocyanate (AITC; also known as mustard oil) or capsaicin. The threshold for each compound was determined for each subject. The results of the NMP measurements were evaluated in parallel with the therapeutic response, visual analog scale scores for nasal symptoms, self-reported NHR, and mRNA expression of PGP9.5; TRPV1; transient receptor potential cation channel subfamily A, receptor 1 (TRPA1); TRPV4; transient receptor potential cation channel subfamily M, member 8 (TRPM8); and nerve growth factor (NGF) in nasal biopsy specimens. Results: AITC turned out to be the best stimulus because the coughing induced by capsaicin interfered with measurements. At baseline, the threshold for evoking changes in NMPs based on AITC was significantly lower for patients with IR compared with HC subjects (P = .0423). Capsaicin treatment of IR patients increased the threshold for the response to AITC at 4 and 12 weeks compared with placebo (P = .0406 and P = .0325, respectively), which returned to baseline by week 26 (P = .0611). This increase correlated with changes in visual analog scale major symptom (P = .0004) and total symptom (P = .0018) scores. IR patients with self-reported NHR at baseline showed a trend to being better responders to capsaicin treatment compared with patients with IR but without NHR (P = .10). Conclusion: The lower threshold for AITC based on NMPs in patients with IR compared with HC subjects and the increased threshold for AITC after capsaicin treatment in patients with IR demonstrate the crucial role of TRPA1 and TRPV1 in IR pathophysiology. The strong correlation between the increase in AITC threshold in patients with IR and symptom reduction after capsaicin treatment demonstrates the clinical relevance of these findings.

Objectives/Hypothesis Empty nose syndrome (ENS) is a controversial disorder and the change of histopathology has never been discussed. This study aimed to conduct a structured histological review to improve the diagnosis and understanding of ENS. Further immunohistochemical staining of transient receptor potential channel melastatin 8 (TRPM8) was performed. Study Design A prospective case-control study in a tertiary medical center. Methods Consecutive patients with ENS who were diagnosed and received surgical intervention after failure of conservative management were included. Patients with benign pituitary gland tumor receiving transsphenoidal excision were enrolled as control group. Biopsy of inferior turbinate was obtained during surgery for histological review and immunohistochemical staining. Results Seventeen patients with ENS and six patients as a control group were established for structured histological review. Patients with ENS presented significantly more squamous metaplasia, a higher rate of submucosal fibrosis, and a lower submucosal gland number grading. Additionally, a unique histological change called goblet cell metaplasia was found in the ENS group. The respiratory epitheliums of ENS were mostly intact with preservation of ciliated cells and goblet cells. The ENS group had a significantly lower expression level of TRPM8. Conclusions The nasal mucosa of ENS experienced some airway remodeling and thermoreceptors downregulation, which contribute to clinical symptoms. The distinct histology of ENS included preserved respiratory epithelium and goblet cell metaplasia, accompanying with characteristics similar to atrophic rhinitis. Biopsy of the inferior turbinate may help diagnose ENS. Level of Evidence 4 Laryngoscope, 2020