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Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats

1
Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
2
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
3
Anapn Korean Traditional Medical Clinic, 11, Seongnae-ro, Gangdong-gu, Seoul 05392, Korea
4
Department of Physiology, School of Medicine, Kyung Hee University, Seoul 02447, Korea
5
Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
*
Authors to whom correspondence should be addressed.
Toxins 2019, 11(7), 396; https://doi.org/10.3390/toxins11070396
Received: 6 June 2019 / Revised: 28 June 2019 / Accepted: 2 July 2019 / Published: 8 July 2019
(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)
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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. View Full-Text
Keywords: chemotherapy; cold allodynia; mechanical allodynia; melittin; neuropathic pain; oxaliplatin chemotherapy; cold allodynia; mechanical allodynia; melittin; neuropathic pain; oxaliplatin
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Choi, S.; Chae, H.K.; Heo, H.; Hahm, D.-H.; Kim, W.; Kim, S.K. Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats. Toxins 2019, 11, 396.

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