TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNEL: AN EMERGING TARGET FOR PAIN

Pain perception begins with the activation of primary sensory nociceptors. Over the past decade, flourishing research has revealed that members of the Transient Receptor Potential (TRP) ion channel family are fundamental molecules that detect noxious stimuli and transduce a diverse range of physical and chemical energy into action potentials in somatosensory nociceptors. Here we highlight the roles of TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8), TRP vanilloid 3 (TRPV3) and TRP vanilloid 4 (TRPV4) in the activation of nociceptors by heat and cold environmental stimuli, mechanical force and by chemicals including exogenous plant and environmental compounds as well as endogenous inflammatory molecules. The contribution of these channels to pain and somatosensation is discussed at levels ranging from whole animal behavior to molecular modulation by intracellular signaling proteins. An emerging theme is that TRP channels are not simple ion channel transducers of one or two stimuli, but instead serve as promising drug targets for the management of pain. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. This review focuses on summarizing the evidence that modulation of selected TRP channels may have beneficial effects in pain management.