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

Yıl 2018, Cilt: 10 Sayı: 3, 789 - 789, 18.08.2018

Mustafa Kemal Yıldırım

https://doi.org/10.37212/jcnos.610118

Öz

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 (Nazıroğlu 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. Itseems to that the exact relationship between TRP channel activation and chemotherapeutic agents still remain to be determined.

Anahtar Kelimeler

TRP channel, Pain, Calcium ion, Oxaliplatin, Oxidative stress

Kaynakça

• Materazzi S, Fusi C, Benemei S, Pedretti P, Patacchini R, Nilius B, Prenen J, Creminon C, Geppetti P, Nassini R. 2012. TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch. 2012 463:561-9.
• Medvedeva YV, Kim MS, Usachev YM. 2008. Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons. J Neurosci. 28:5295-5311.
• Nazıroğlu M, Braidy N. 2017. Thermo-Sensitive TRP Channels: Novel Targets for Treating Chemotherapy-Induced Peripheral Pain. Front Physiol. 8:1040.
• Uchida K, Dezaki K, Yoneshiro T, Watanabe T, Yamazaki J, Saito M. 2017. Involvement of thermosensitive TRP channels in energy metabolism. J Physiol Sci. 67:549-560.