TRPV1, also known as the capsaicin receptor, is a non-selective cation channel. It is expressed by a subset of peripheral sensory neurons involved in pain sensation and at other neuronal and non-neuronal sites in the mammalian body. Functionally, it acts as a sensor for noxious heat (above ~42 °C), and can be activated by endogenous lipid-derived molecules, acidic solutions (pH < 6.5), pungent chemicals like capsaicin, and toxins. Structurally, TRPV1 subunits have six transmembrane domains with intracellular N-and C-termini and a pore region. It plays a role in pain, thermoregulation, osmoregulation, cough, and overactive bladder [1].

Studies with Trpv1 (- / -) mice have been crucial. They suggest that TRPV1 is involved in pain, thermoregulation, and osmoregulation. For example, TRPV1 activation has been associated with chronic inflammatory pain and peripheral neuropathy. Its expression in non-neuronal areas like the bladder, lungs, and cochlea is responsible for the development of cystitis, asthma, and hearing loss [1,3]. In cutaneous TRPV1+ neurons, their activation can elicit a local type 17 immune response that augments host defense to certain pathogens [2]. TRPV1 blockers show effectiveness in animal models of psychiatric disorders, reducing anxiety, fear, and despair, but their development is limited by effects on body temperature, especially hyperthermia [4].

In conclusion, TRPV1 is a key molecule in sensing noxious stimuli and is involved in multiple biological processes and disease conditions. The use of Trpv1 knockout mouse models has significantly enhanced our understanding of its role in pain, thermoregulation, immunity, and various diseases such as chronic pain, bladder disorders, and psychiatric disorders, providing potential targets for therapeutic intervention.

References:

1. Bevan, Stuart, Quallo, Talisia, Andersson, David A. . TRPV1. In Handbook of experimental pharmacology, 222, 207-45. doi:10.1007/978-3-642-54215-2_9. https://pubmed.ncbi.nlm.nih.gov/24756708/

2. Cohen, Jonathan A, Edwards, Tara N, Liu, Andrew W, Albers, Kathryn M, Kaplan, Daniel H. 2019. Cutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity. In Cell, 178, 919-932.e14. doi:10.1016/j.cell.2019.06.022. https://pubmed.ncbi.nlm.nih.gov/31353219/

3. Aghazadeh Tabrizi, Mojgan, Baraldi, Pier Giovanni, Baraldi, Stefania, Merighi, Stefania, Borea, Pier Andrea. 2016. Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists. In Medicinal research reviews, 37, 936-983. doi:10.1002/med.21427. https://pubmed.ncbi.nlm.nih.gov/27976413/

4. Iglesias, Lia P, Aguiar, Daniele C, Moreira, Fabrício A. . TRPV1 blockers as potential new treatments for psychiatric disorders. In Behavioural pharmacology, 33, 2-14. doi:10.1097/FBP.0000000000000603. https://pubmed.ncbi.nlm.nih.gov/33136616/