TRPV1: A Potential Drug Target for Treating Various Diseases

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is an ion channel present on sensory neurons which is activated by heat, protons, capsaicin and a variety of endogenous lipids termed endovanilloids. As such, TRPV1 serves as a multimodal sensor of noxious stimuli which could trigger counteractive measures to avoid pain and injury. Activation of TRPV1 has been linked to chronic inflammatory pain conditions and peripheral neuropathy, as observed in diabetes. Expression of TRPV1 is also observed in non-neuronal sites such as the epithelium of bladder and lungs and in hair cells of the cochlea. At these sites, activation of TRPV1 has been implicated in the pathophysiology of diseases such as cystitis, asthma and hearing loss. Therefore, drugs which could modulate TRPV1 channel activity could be useful for the treatment of conditions ranging from chronic pain to hearing loss. This review describes the roles of TRPV1 in the normal physiology and pathophysiology of selected organs of the body and highlights how drugs targeting this channel could be important clinically.

Transient Receptor Potential Vanilloid 1 Involvement in Animal Pain Perception

“…The increasing interest on TRPV1 is not only the role of this channel in mediating inflammatory and chronic pain (Re et al, 2007), but also is involvement in a huge number of pathologies (especially oncology) and diseases ranging from diabetes and urinary incontinence to arthritis and hearing loss (Bley, 2004;Brito et al, 2014). However, although the compounds used in clinical trials, the therapeutic utility of TRPV1 agonist and antagonists is yet to be validated unequivocally, both for humans and animals.…”

“…Anyway it is important to underlie that the local application leads to a burning sensation and erythema, but few serious side effects (Spruce et al, 2003;Galluzzi et al, 2007;Brito et al, 2014). Capsaicin application also produces a release of substance P and CGRP in the skin and it is possible that continued application of capsaicin depletes peripheral terminals of these pro-nociceptive substances (Kwak, 2012).…”

“…The first reported TRPV1 antagonist, capsazepine, was discovered by modifying the chemical backbone of capsaicin (Walpole et al, 1994). Capsazepine competes for the capsaicin-binding site on TRPV1, blocks capsaicin-induced channel activation in neonatal rat dorsal root ganglion (Brito et al, 2014).…”

A novel analgesic approach to optogenetically and specifically inhibit pain transmission using TRPV1 promoter

“…TRPV1 plays an important role in the development of chronic pain, especially inflammatory pain (Caterina et al, 2000;Davis et al, 2000;Walder et al, 2012), and can be sensitized by a number of inflammatory mediators under pathological conditions (Amadesi et al, 2004;Moriyama et al, 2005). In addition, TRPV1 has been found expressed in non-neuronal cells such as epithelium cells in the lung and hair cells of the cochlea, therefore involved in the pathophysiology of multiple diseases such as asthma and hearing loss (Brito et al, 2014). The critical regulatory elements of TRPV1 gene promoter is controlled by the first 2 kb upstream of the Transcription Start Site (TSS), which contains a conserved INR sequence (Chu et al, 2011;Xue et al, 2007).…”

“…Transient Receptor Potential Vanilloid channel type 1 (TRPV1) is a non-selective cation channel that is activated by heat (443 1C), protons (pHo5.9), chemicals such as capsaicin, and is widely expressed in peripheral nociceptive neurons (Caterina et al, 1997;Caterina and Julius, 2001) as well as in the central nervous system and other tissues (Cavanaugh et al, 2011;Brito et al, 2014). TRPV1 plays an important role in the development of chronic pain, especially inflammatory pain (Caterina et al, 2000;Davis et al, 2000;Walder et al, 2012), and can be sensitized by a number of inflammatory mediators under pathological conditions (Amadesi et al, 2004;Moriyama et al, 2005).…”