The α9α10 Nicotinic Acetylcholine Receptor Antagonist αO-Conotoxin GeXIVA[1,2] Alleviates and Reverses Chemotherapy-Induced Neuropathic Pain.

Huanbai Wang,Sulan Luo,Dongting Zhangsun,Xiaodan Li,Ruibin Su,Gang Yu

doi:10.3390/md17050265

Abstract

Oxaliplatin is a third-generation platinum drug and is widely used as a first-line therapy for the treatment of colorectal cancer (CRC). However, a large number of patients receiving oxaliplatin develop dose-limiting painful neuropathy. Here, we report that αO-conotoxin GeXIVA[1,2], a highly potent and selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype, can relieve and reverse oxaliplatin-induced mechanical and cold allodynia after single and repeated intramuscular (IM) injections in rats. Treatments were started at 4 days post oxaliplatin injection when neuropathic pain emerged and continued for 8 and 16 days. Cold score and mechanical paw withdrawal threshold (PWT) were detected by the acetone test and von Frey test respectively. GeXIVA[1,2] significantly relieved mechanical and cold allodynia in oxaliplatin-treated rats after a single injection. After repeated treatments, GeXIVA[1,2] produced a cumulative analgesic effect without tolerance and promoted recovery from neuropathic pain. Moreover, the long lasting analgesic effect of GeXIVA[1,2] on mechanical allodynia continued until day 10 after the termination of the 16-day repeated treatment procedure. On the contrary, GeXIVA[1,2] did not affect acute mechanical and thermal pain behaviors in normal rats after repeated injections detected by the von Frey test and tail flick test. GeXIVA[1,2] had no influence on rat hind limb grip strength and body weight after repeated treatments. These results indicate that αO-conotoxin GeXIVA[1,2] could provide a novel strategy to treat chemotherapy-induced neuropathic pain.

Highlights

Cancer is a major threat to human health, and chemotherapy is one of the most effective treatments.a variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment [1].few strategies are available for treating this kind of neuropathy, partially due to the complexity of its pathogenesis [2]
The present study aimed to discover the possibility of applying GeXIVA[1,2] to control oxaliplatin-induced neuropathic pain
Distinct from neuropathic pain induced by trauma and disease, chemotherapy-induced neuropathic is commonly a predictable outcome cancer to its high incident

Summary

Introduction

Cancer is a major threat to human health, and chemotherapy is one of the most effective treatments.a variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment [1].few strategies are available for treating this kind of neuropathy, partially due to the complexity of its pathogenesis [2]. Cancer is a major threat to human health, and chemotherapy is one of the most effective treatments. A variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment [1]. Few strategies are available for treating this kind of neuropathy, partially due to the complexity of its pathogenesis [2]. It has great significance to develop analgesic drugs with novel mechanisms. Mar. Drugs 2019, 17, 265; doi:10.3390/md17050265 www.mdpi.com/journal/marinedrugs

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