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

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.

• Authors: Huanbai Wang, Xiaodan Li, Dongting Zhangsun, Gang Yu, Ruibin Su, Sulan Luo
• Journal: Marine drugs (Mar Drugs) Vol. 17 Issue 5 (May 05 2019) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 31060282 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Conotoxins
• alpha-conotoxin, Conus generalis
• Oxaliplatin

Topics

• Analgesics (pharmacology)
• Animals
• Conotoxins (pharmacology)
• Disease Models, Animal
• Hyperalgesia (drug therapy)
• Male
• Neuralgia (chemically induced, drug therapy)
• Oxaliplatin (administration & dosage, adverse effects, antagonists & inhibitors)
• Rats
• Rats, Sprague-Dawley