Supraspinal Transient Receptor Potential Subfamily V Member 1 (TRPV1) in Pain and Psychiatric Disorders

Abstract

The transient receptor potential subfamily V member 1 (TRPV1) belongs to the diverse transient receptor potential (TRP) family of cation channels. It was first characterized in primary afferent fibres as a receptor for capsaicin. Peripheral TRPV1 has a very well-described role in nociception. However, TRPV1 is now recognized to have a broader distribution and function, with supraspinal/brain TRPV1 known to modulate pain processing. Recently, studies employing histological, genetic and pharmacological approaches have provided evidence that supraspinal TRPV1 also modulates brain neurobiology and behaviours related to anxiety, depression and schizophrenia. Key brain regions involved in TRPV1-mediated modulation of pain and affect include the periaqueductal grey, hippocampus and medial prefrontal cortex. Thus, TRPV1 in the brain is emerging as an important molecular substrate which is dually implicated in both pain and psychiatric disorders, and represents a novel therapeutic target for these conditions and their comorbidity.

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Finding an appropriate antibody against TRPV1 to use in the western blotting study was a challenge. A number of papers have questioned the presence of TRPV1 in the brain (Fogaça et al, 2012;Madasu et al, 2015;Martins et al, 2014). However, recently, Navarria et al, demonstrated that TRPV1 is present in the hippocampus, and is upregulated in Wistar rats exposed to restraint stress (Navarria et al, 2014).…”

Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1

“…While some studies have demonstrated anti-inflammatory effects of AEA on TLR4-induced inflammatory responses to be mediated by cannabinoid CB1 and/or CB2 receptor activation and consequential regulation of NFκB and MAPK activation (Correa et al, 2009a;Correa et al, 2010;Krishnan et al, 2012;Ortega-Gutierrez et al, 2005), non-CB1/CB2 receptor mediated effects of AEA on inflammatory processes in vitro have also been reported (Correa et al, 2008;Tham et al, 2007). AEA also has affinity for and activity at additional receptor targets to CB1 and CB2 receptors, namely the peroxisome proliferator-activated receptors (PPARs), the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and also the novel cannabinoid receptor, G-protein coupled receptor (GPR)55 [for reviews see (Alexander and Kendall, 2007;Di Marzo et al, 2001;Madasu et al, 2015;O'Sullivan and Kendall, 2010)], activity at which may account for the variability in the effects of AEA on neuroinflammatory responses following TLR activation.…”

NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice

“…It has been shown that 494 TRPV1 channels are expressed in dopaminergic neurons 495 in the several regions of the brain including hippocampus 496 and cortical areas (Cristino et al, 2006;Edwards, 2014). 497 Activation of TRPV1 channels is known to induce depolar-498 ization in the neurons through enhancing the calcium 499 influx (Madasu et al, 2015). In this regard, a study by rodents (Koltunowska et al, 2013;Belujon et al, 2015;527 Fuller et al, 2015).…”