TRPV1: On the Road to Pain Relief

Abstract

Historically, drug research targeted to pain treatment has focused on trying to prevent the propagation of action potentials in the periphery from reaching the brain rather than pinpointing the molecular basis underlying the initial detection of the nociceptive stimulus: the receptor itself. This has now changed, given that many receptors of nociceptive stimuli have been identified and/or cloned. Transient Receptor Potential (TRP) channels have been implicated in several physiological processes such as mechanical, chemical and thermal stimuli detection. Ten years after the cloning of TRPV1, compelling data has been gathered on the role of this channel in inflammatory and neuropathic states. TRPV1 activation in nociceptive neurons, where it is normally expressed, triggers the release of neuropeptides and transmitters resulting in the generation of action potentials that will be sent to higher CNS areas where they will often be perceived as pain. Its activation also will evoke the peripheral release of pro-inflammatory compounds that may sensitize other neurons to physical, thermal or chemical stimuli. For these reasons as well as because its continuous activation causes analgesia, TRPV1 has become a viable drug target for clinical use in the management of pain. This review will provide a general picture of the physiological and pathophysiological roles of the TRPV1 channel and of its structural, pharmacological and biophysical properties. Finally, it will provide the reader with an overall view of the status of the discovery of potential therapeutic agents for the management of chronic and neuropathic pain.

20-Hydroxyeicosatetraenoic Acid (20-HETE) Is a Novel Activator of Transient Receptor Potential Vanilloid 1 (TRPV1) Channel

“…In hTRPV1-transfected HEK cells responses to both 20-HETE and capsaicin underwent desensitization, a phenomenon consistent with the known activity of capsaicin and other agents that directly gate channel opening (3, 20). Assessment of 20-HETE effects in excised patches demonstrated an apparent delayed 20-HETE-evoked channel opening (supplemental Fig.…”

Capsaicin Used on Skin Influences Ion Transport Pathways: An in vitro Study

“…Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a lipophilic alkaloid found in hot red chili peppers of the genus Capsicum (hot chili peppers), has long been used to treat persistent pain, such as osteoarthritic pain, postherpetic neuralgia of the trigeminal nerve, cluster headache, diabetic neuropathy, HIV-associated distal sensory neuropathy, and intractable pain in cancer patients [1,2,3,4,5,6,7,8,9,10,11,12]. Capsaicin is an agonist of transient receptor potential cation channel, subfamily V, member 1 (TRPV1), which provides the sensation of pain (nociception).…”

The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized Neuropathic Pain, and Clinical Evidence Supporting its Use

“…Another probable mechanism is direct activation of the TRP (transient receptor potential) channels TRPV1 and TRPA1 expressed in nociceptive sensory neurons. This produces analgesia by membrane depolarization, reducing the electrical activity in TRP-containing nerves [28]. …”