• Kyoji Taguchi.
• Departments of Medicinal Pharmacology, Showa Pharmaceutical University.
• Yakugaku Zasshi. 2016 Jan 1; 136 (2): 287-96.

AbstractPeripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles. Although many basic and clinical researchers have studied anticancer drug-induced peripheral neuropathy, the mechanism is not well understood. In this review, we focus on (1) analysis of transient receptor potential vanilloid 1 (TRPV1) channel expression in the rat dorsal root ganglion (DRG) after paclitaxel treatment and (2) analysis of transient receptor potential ankyrin 1 (TRPA1) channel in the DRG after oxaliplatin treatment. This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium-diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen-activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy.

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