Transient Receptor Potential Vanilloid 1 Agonists as Candidates for Anti-inflammatory Agents

Abstract

The transient receptor potential vanilloid-1 (TRPV1) cation channel is a receptor that is activated by heat, acidosis and a variety of chemicals, including capsaicin. With these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurons. As many proalgesic pathways converge on TRPV1 and it is upregulated and sensitized by inflammation and injury, TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for the pharmacological control of pain. However, there is conflicting evidence to date as to whether TRPV1 agonists promote or inhibit inflammation. We recently demonstrated that SA13353 [1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea], a novel TRPV1 agonist, inhibits tumor necrosis factor-α production through the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms of kidney injury, lung inflammation, arthritis and encephalomyelitis in disease models. These results suggest that TRPV1 agonists may act in an anti-inflammatory manner in vivo in certain inflammatory diseases.