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

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.Rec.