Abstract
Oxaliplatin, which is widely used in treating cancers such as colorectal cancer, frequently causes peripheral neuropathy. It not only significantly reduces the patient's quality of life due to physical distress but may also result in a change or discontinuation of cancer treatment. Oxaliplatin-induced peripheral neuropathy (OIPN) is classified as acute or chronic depending on the onset time of side effects; however, the prevention and treatment of OIPN has not been established. As these peripheral neuropathies are side effects that occur due to treatment, the administration of effective prophylaxis can effectively prevent their onset. Although transient relief of symptoms such as pain and numbness enable the continuation of cancer treatment, it may result in the worsening of peripheral neuropathy. Thus, understanding the pathological mechanisms of OIPN and finding better preventative measures are important. This review focuses on animal models to address these issues, clarifies the pathological mechanisms of OIPN, and summarizes various approaches to solving OIPN, including targets for preventing OIPN.
Highlights
Anticancer drugs, such as vinca alkaloids, taxanes, platinum derivatives, and bortezomib are commonly used in cancer chemotherapy; they typically induce peripheral neuropathy, characterized by numbness and pain in the limbs
This review focuses on oxaliplatin-induced peripheral neuropathy (OIPN), which is of particular concern in clinical practice
Memantine, an NMDA receptor antagonist, and ifenprodil and trifloperazine, which have NMDA receptor subtype 2B (NR2B) and calmodulin inhibitory effects, respectively, suppressed calmodulin-dependent protein kinase II (CaMKII) activity and temporarily improved mechanical allodynia. These findings suggest that the NR2B-mediated activation of nitric oxide synthase (NOS) and CaMKII is involved in oxaliplatin-induced mechanical allodynia
Summary
Anticancer drugs, such as vinca alkaloids (e.g., vincristine, vinorelbine, and vinblastine), taxanes (e.g., paclitaxel and docetaxel), platinum derivatives (oxaliplatin and cisplatin), and bortezomib are commonly used in cancer chemotherapy; they typically induce peripheral neuropathy, characterized by numbness and pain in the limbs. Oxalate is involved in cold allodynia, an acute peripheral neuropathy, which can be caused by oxaliplatin. A significant increase in extracellular glutamate levels and a decrease in glutamate transporter 1 expression were observed in the spinal cord of rats during the development of mechanical allodynia induced by oxaliplatin [19].
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