Involvement of Thermo TRP channels on chemothrepeutic agents-induced peripheral pain

Abstract

Accumulating evidences have indicated that  disturbances in intracellular free calcium ([Ca2+]i)  concentration play an important role in the  pathophysiology of peripheral pain. Ca2+ passes cell  membrane via different channels such as chemical and  voltage gated channels. Apart from the well-known  cation channels, there is recently discovered channels  namely transient receptor potential (TRP) family. At  least, 11 TRP channels in mammalian cells have been  identified as thermosensitive TRP (thermo-TRP)  channels (Uchida et al. 2017). Two TRP channels  (TRPV1 and TRPV2) are activated by high  temperatures. Five TRP channels (TRPV1-4 and  TRPM2) are activated by different heat temperatures,  although two of TRP channels (TRPA1 and TRPM8)  are activated by cold and cool temperatures,  respectively (Naziroglu and Braidy, 2017). It is well  known that increase of [Ca2+]i concentration but  decrease of intracellular Mg2+ levels induces activation  of nitric oxide synthase (NOS) enzyme. By catalytic  activity of NOS, nitric oxide synthetizes in neurons. In  turn, it induces pain through production of excitatory  amino acids and substance P (Medvedeva et al. 2008).  Results of recent studies indicated involvement of  chemothrepeutic agents (i.e. cisplatin, oxaliplatin and  paclitaxel)-induced mitochondrial oxidative stress  through activation of Thermo TRP channels such as  TRPA1, TRPV1 and TRPM8, although antioxidants  induced protective action on the pain induction through  inhibition of the TRP channels in the experimental  animals (Materazzi et al. 2012). In the oral presentation,  I discussed novel effects of chemotherapeutic agents on  the peripheral pain by the regulation of TRP channels.  I concluded that the chemotherapeutic agents  cause TRP channel activation and oxidative stress,  which may lead to the pathology of peripheral pain. It seems to that the exact relationship between TRP  channel activation and chemotherapeutic agents still  remain to be determined.