Thermo-TRP Channels in Pain Sensation

Important conceptual changes concerning human thermoregulation have revealed in the last decade. Recent investigations in central and peripheral thermosensitivity have emphasized the importance of temperature-activated transient receptor potential (TRP) cation channels and they are being ardently pursued as targets for analgesic drug discovery. They are the largest group of sensory detectors expressed in nerve terminals and pain receptors activated by temperature and provide information about thermal changes in the environment. Thermo-TRP channels are capable of initiating sensory nerve impulses following the detection of thermal, as well as mechanical and chemical irritant stimuli. At least, a family of six thermo-TRP channels has been characterized to date (TRPA1, TRPM8, TRPV1, TRPV2, TRPV3, and TRPV4) that exhibit sensitivity to increases or decreases in temperature as well as to chemical substances that elicit similar hot or cold sensations. Such irritants include menthol, cinnamaldehyde, gingerol, capsaicin, mustard oil, camphor, eugenol, and others. The thermal thresholds of many thermo-TRP channels are known to be modulated by extracellular mediators, released by tissue damage or inflammation, such as bradykinin, prostaglandins, and growth factors. Antagonists or blockers of these channels are likely as promising targets for new analgesic drugs at the periphery and central levels and thus, controlling the modulation of thermo-TRP channels by inflammatory mediators and ligands may be a useful alternative strategy in developing novel analgesics.