Interactions between chemotherapy-induced neuropathic pain and TRPV1 channel

Abstract

As a complex problem, pain activates several conditions, symptoms, and molecular pathways. After stimulation of a nociceptors, action potentials are generated and then propagated to the brain, resulting in a sensation of pain is induces through production and propagation of action potential. Most efficient way to treat chronic pain is with opioids, however the drugs of opioid system induce several adverse effects such as addictive behavior and desensitization. Chemotherapeutic agent (such as oxaliplatin, cisplatin, paclitaxel)-based anticancer drugs cause neurotoxicity through excessive calcium ion (Ca2+) influx. Peripheral neuropathies are a common side effect of treatment of various chemotherapeutics. Today, targeting the cation channels and excessive Ca2+ influx that contribute to the detection of stimuli may be an effective approach in treating chemotherapeutic agents-induced pain syndromes. Several physiological and pathophysiological functions are induced by excessive Ca2+ influx. The Ca2+ passes the cell membrane through several channels such as voltage gated calcium channels (VGCC) and chemical (ligand) channels. In addition to the well-known VGCC and ligand channel, new channels namely transient receptor potential (TRP) channels were discovered within last decades. The TRP superfamily is including 28 members in mammalian and a member of the TRP superfamily is TRP vanilloid 1 (TRPV1) channels. The TRPV1 channel is activated by several stimuli including hot chili pepper component (capsaicin), heat, acidic pH and oxidative stress (Caterina et al. 1997). Expression levels of TRPV1 channel is high in dorsal root ganglion (DRG) and it is mainly responsible from neuropathic pain (Naziroglu and Braidy, 2017; Muller et al.  2019). Therefore, TRPV1 channel has great importance in the chemotherapy-induced neuropathic pain induction. In the current study, I will summarize present reports on the TRPV1 channel in literature. as novel target for treating chemotherapy-induced peripheral pain. In addition, I will summarize future directions of the novel targets.