INVOLVEMENT OF TRPM2 AND TRPV1 ON CHEMO THERAPEUTIC AGENTS-INDUCED PERIPHERAL PAIN

Abstract

Neuropathic pain has a tremendous impact on quality of life in diseases such as diabetes and cancer. One of the symptoms of this disorder might be pain and it ultimately progresses to marked degeneration of the peripheral nerves. Abnormal Ca²⁺ channel physiology and expression have been implicated in a number of pain states in cancer treatment with chemotherapeutic drugs. The TRPM2 channel is activated by poly (ADP-ribose) polymerase (PARP) pathways through the production of ADP-ribose and oxidative stress. The TRPV1 is activated by hot chili pepper component (capsaicin) and reactive oxygen species (ROS) (1). The expression levels of TRPM2 and TRPV1 are high in the DRG neuron (2). ROS acts a central role in chemotherapeutic drug-induced dorsal root ganglion (DRG) death and peripheral pain (3).

Selenium is strong antioxidant trace element in cisplatin-induced oxidative stress (3). Recently we observed modulator role of selenium on apoptosis, oxidative stress and calcium entry through TRPM2 and TRPV1 channels in DRG neuron of fibromyalgia-induced rats (3). Recently, I observed similar protective effects of selenium in the oxaliplatin, paclitaxel and cisplatin-induced neuropathic pain of rats and mice, although there was no pain in the TRPM2 knockout mice. In the recent unpublished results, chemotherapeutic agent-based anticancer drugs caused neurotoxicity through excessive apoptosis, mitochondrial oxidative stress and overload Ca²⁺ entry. In this presentation, I will summarize our and other recent experimental research findings on how these chemotherapeutic drug-induced oxidative stresses, TRPM2 and TRPV1 activations are regulated in peripheral pain by antioxidants such as selenium.

In conclusion, the results indicate that oxaliplatin, cisplatin and paclitaxel-induced TRPM2 and TRPV1 channels activation can result in remarkable peripheral pain induction effects through excessive oxidative stress and overload Ca²⁺ entry in the DRG neurons of rats.

Keywords: Cisplatin; Oxaliplatin; Oxidative stress; Peripheral pain; Selenium; TRP Channel.

References

1. Nazıroğlu M and Braidy N (2017) Thermo-sensitive TRP channels: Novel targets for treating chemotherapy-induced peripheral pain. Front. Physiol. 8:1040.

2. Akpınar H, Nazıroğlu M, Övey İS, Çiğ B, Akpınar O. The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 2016;22;6:37196.3. Yüksel E, Nazıroğlu M, Şahin M, Çiğ B. Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium. Sci Rep. 2017;7:17543.