Abstract

Oxaliplatin is a chemotherapeutic agent used for metastatic colon and other advanced cancers. Most common side effect of oxaliplatin is peripheral neuropathy, manifested in mechanical and cold allodynia. Although the analgesic effect of bee venom has been proven to be effective against oxaliplatin-induced peripheral neuropathy, the effect of its major component; melittin has not been studied yet. Thus, in this study, we investigated whether melittin has an analgesic effect on oxaliplatin-induced allodynia. Intraperitoneal single injection of oxaliplatin (6 mg/kg) induced mechanical and cold allodynia, resulting in increased withdrawal behavior in response to von Frey filaments and acetone drop on hind paw. Subcutaneous melittin injection on acupoint ST36 (0.5 mg/kg) alleviated oxaliplatin-induced mechanical and cold allodynia. In electrophysiological study, using spinal in vivo extracellular recording, it was shown that oxaliplatin-induced hyperexcitation of spinal wide dynamic range neurons in response to peripheral stimuli, and melittin administration inhibited this neuronal activity. In behavioral assessment, analgesic effect of melittin was blocked by intrathecal α1- and α2- adrenergic receptor antagonists administration. Based on these results, we suggest that melittin could be used as an analgesic on oxaliplatin-induced peripheral neuropathy, and that its effect is mediated by activating the spinal α1- and α2-adrenergic receptors.

Highlights

  • Oxaliplatin is the third-generation platinum based chemotherapeutic agent, which is combined with fluorouracil and leucovorin for metastatic colorectal cancer [1]

  • We suggest that melittin could be used as an analgesic on oxaliplatin-induced peripheral neuropathy, and that its effect is mediated by activating the spinal α1- and α2-adrenergic receptors

  • The results of the present study demonstrate that melittin administration on ST36 can relive the mechanical and cold allodynia induced by a single injection of oxaliplatin in rats

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Summary

Introduction

Oxaliplatin is the third-generation platinum based chemotherapeutic agent, which is combined with fluorouracil and leucovorin for metastatic colorectal cancer [1]. Oxaliplatin treatment can induce peripheral neuropathy expressed in sensitivity to cold, numbness and tingling in hands and feet [4,5]. These sensory neuropathies have long been recognized as the major dose-limiting adverse events of oxaliplatin treatment [6]. Several agents showed potentiality to prevent and treat oxaliplatin-induced peripheral neuropathy [7,8]. These agents have limitations including side effects such as fatigue, insomnia, and nausea [8]

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