Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.

Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and polymodal sensor of noxious heat, protons, capsaicin and endogenous lipids. The wide variety of functions of TRPV1 in pain transmission, inflammatory pathways and neurological disorders has triggered efforts to understand the molecular mechanisms underlying these functions, particularly pain and neuroinflammation. The molecular structure and its tetrameric structure, temperature and ligand dependent activation and post-translational modification are discussed. It also covers the Ca2⁺-dependent signalling pathways such as CaMKII/Nrf2, MAPK, NF-κB and PI3K/ERK, and the localization of TRPV1 in sensory neurons, microglia, astrocytes, T lymphocytes and brain tissues. Other notable mentions are the involvement of TRPV1 in acute inflammatory, neuropathic, and visceral pain as well as in neuroinflammatory and neurodegenerative diseases like multiple sclerosis, Alzheimer's disease and Parkinson's disease. Evidence that comes from the various studies suggests that TRPV1 may cause a number of different responses depending on the cell and disease context, whether pro-inflammatory or neuroprotective. Therapeutic strategies directed to TRPV1 such as desensitizing agents, allosteric and state-selective modulators, peptide-based and natural-product based ligands, and gene-directed strategies, are also taken into account. To conclude, the context-dependent activity of TRPV1 signalling holds promise for therapeutic applications, and highlights the importance for context-specific, local and precise targeting of TRPV1 in clinical practice.