RESUMEN
BACKGROUND: Transient Receptor Potential (TRP) channels are non-selective Ca2+ permeable channels with a wide and dynamic involvement in the perception of environmental stimuli in the oral cavity and a pivotal role in oral tissues' pathology and oral diseases. Several factors secreted during pulpitis and periodontitis, such as pro-inflammatory cytokines, prostaglandins, glutamate, extracellular ATP, and bradykinin, can trigger TRPs, either directly or indirectly, lowering the threshold of sensory neurons and regulate immune cell function. OBJECTIVE: To investigate the diverse functions and molecular mechanisms of TRP channels in oral pathology and critically discuss their clinical significance and therapeutic targeting potential. METHODS: Relevant keywords were used for research in scientific databases (Pumped, Scopus, and Science Direct). Only articles in English were included, screened, and critically analyzed. The key findings of these studies were included, along with their clinical importance. RESULTS: Certain TRP channels were detected as key mediators of oral pathology. TRPV1 was revealed to play an important role in pain transduction in pulpits, induce inflammation, and be involved in bone resorption during periodontitis. TRPM2 activation may reduce saliva secretion in acinar salivary cells and xerostomia after head and neck radiation, while TRPV1 and TRPA1 channels mediate trigeminal nerve pain. Several TRP agonists and antagonists have been demonstrated to block pathological pathways in oral diseases along with certain compounds such as capsaicin, capsazepine, nifedipine, eugenol, thapsigargin and specific targeting techniques such as UHF-USP and Er: YAG lasers. Current TRP targeting approaches have been shown to exert beneficial effects in osteoblasts and fibroblasts proliferation, carcinoma cells' apoptosis, saliva secretion, and nociception. CONCLUSION: TRPs play a central role in pain transduction, inflammatory responses in oral tissues, and pathological conditions of the oral mucosa, including oral squamous cell carcinoma and ulcerative mucositis.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Neuralgia , Canales de Potencial de Receptor Transitorio , Humanos , Canales de Potencial de Receptor Transitorio/metabolismo , Patología Bucal , Canales Catiónicos TRPVRESUMEN
BACKGROUND: Oropharyngeal dysphagia (OD) treatment is moving away from compensatory strategies toward active treatments that improve swallowing function. The aim of this study was to assess the acute therapeutic effect of TRPA1/M8 agonists in improving swallowing function in OD patients. METHODS: Fifty-eight patients with OD caused by aging, stroke, or neurodegenerative disease were included in a three-arm, quadruple-blind, randomized clinical trial (NCT02193438). Swallowing safety and efficacy and the kinematics of the swallow response were assessed by videofluoroscopy (VFS) during the swallow of 182 ± 2 mPa·s viscosity (nectar) boluses of a xanthan gum thickener supplemented with (a) 756.6 µmol/L cinnamaldehyde and 70 µmol/L zinc (CIN-Zn) (TRPA1 agonists), (b) 1.6 mmol/L citral (CIT) (TRPA1 agonist), or (c) 1.6 mmol/L citral and 1.3 mmol/L isopulegol (CIT-ISO) (TRPA1 and TRPM8 agonists). The effects on pharyngeal event-related potentials (ERP) were assessed by electroencephalography. KEY RESULTS: TRPA1 stimulation with either CIN-Zn or CIT reduced time to laryngeal vestibule closure (CIN-Zn P = .002, CIT P = .023) and upper esophageal sphincter opening (CIN-Zn P = .007, CIT P = .035). In addition, CIN-Zn reduced the penetration-aspiration scale score (P = .009), increased the prevalence of safe swallows (P = .041), and reduced the latency of the P2 peak of the ERP. CIT-ISO had no positive effect on biomechanics or neurophysiology. No significant adverse events were observed. CONCLUSIONS AND INFERENCES: TRPA1 stimulation with CIN-Zn or CIT improves the swallow response which, in the case of CIN-Zn, is associated with a significant improvement in cortical activation and safety of swallow. These results provide the basis for the development of new active treatments for OD using TRPA1 agonists.