Impact of TRP Channels in Oral Pathology and Therapeutic Targeting Options: A Narrative Review

Abstract

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.

Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina

“…Calcium channel blockers can act on different types of channels, such as L, T, N or P/Q channels. Examples of calcium channel blockers are nimodipine, nifedipine and verapamil ( Chen et al, 2022 ; Evangeliou et al, 2023 ).…”