Review ArticleTransient receptor potential vanilloid 1 antagonism in neuroinflammation, neuroprotection and epigenetic regulation: potential therapeutic implications for severe psychiatric disorders treatmentEscelsior, Andreaa,,b; Sterlini, Brunoc,,d; Belvederi Murri, Martinoe; Valente, Pierluigib,,c; Amerio, Andreaa,,b,,f; di Brozolo, Manfredo Radicatig; da Silva, Beatriz Pereiraa,,b; Amore, Marioa,,bAuthor Information aDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa bIRCCS Ospedale Policlinico San Martino cDepartment of Experimental Medicine, University of Genoa dCenter for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia eDepartment of Biomedical and Specialty Surgical Sciences, Institute of Psychiatry, University of Ferrara fMood Disorders Program, Tufts Medical Center, Boston, MA, USA gUniversity of Genoa, Genoa, Italy Received 14 March 2019 Accepted 19 December 2019 Correspondence to Andrea Escelsior, MD, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Ospedale Policlinico San Martino, Section of Psychiatry, University of Genoa, Largo Rosanna Benzi, 10, 16132 Genoa, Italy, Tel: +39 338 7176803; e-mail: firstname.lastname@example.org Psychiatric Genetics: April 2020 - Volume 30 - Issue 2 - p 39-48 doi: 10.1097/YPG.0000000000000249 Buy Metrics Abstract Transient receptor potential vanilloid 1 (TRPV1) is a polymodal cation channel gated by a large array of chemical and physical stimuli and distributed across different brain regions on neuronal and glial cells. Preclinical studies indicate that TRPV1 might be a target for the treatment of anxiety, depression and addictive disorders. The aim of this narrative review is to focus on studies examining the effects of TRPV1 antagonism on neuroinflammation, neuroprotection and epigenetic regulation. Results suggest that TRPV1 modulation leads to pro- or anti-inflammatory effects depending on the cytokine environment and that the TRPV1 antagonism can switch the microglia towards an anti-inflammatory phenotype. Moreover, TRPV1 inhibitors have neuroprotective properties through the regulation of calcium levels. Finally, TRPV1 antagonism exerts regulatory effects on genes involved in synaptic and cognitive functions through histone deacetylase 2 inhibition. These findings highlight different mechanisms that may underlie the efficacy of TRPV1 antagonists in animal models of severe psychiatric disorders. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.