Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats.
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.
['Choi|Seunghwan|S|', 'Chae|Hyeon Kyeong|HK|', 'Heo|Ho|H|', 'Hahm|Dae-Hyun|DH|', 'Kim|Woojin|W|', 'Kim|Sun Kwang|SK|0000-0002-2649-6652']
D058668:Adrenergic alpha-1 Receptor Antagonists D058669:Adrenergic alpha-2 Receptor Antagonists D000700:Analgesics D000818:Animals D000970:Antineoplastic Agents D003080:Cold Temperature D006930:Hyperalgesia D019329:Idazoxan D008555:Melitten D009474:Neurons D000077150:Oxaliplatin D010523:Peripheral Nervous System Diseases D011224:Prazosin D017207:Rats, Sprague-Dawley D018340:Receptors, Adrenergic, alpha-1 D018341:Receptors, Adrenergic, alpha-2 D013116:Spinal Cord D014110:Touch
melittin oxaliplatin cold allodynia chemotherapy mechanical allodynia neuropathic pain