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Toxins 2016, 8(2), 33; doi:10.3390/toxins8020033

Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

1
Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea
2
Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea
3
Yeongju Municipal Hospital, 697 Jangan-ro, Anjeong-myeon, Gyeongsangbuk-do, Yeongju-si 36051, Korea
4
Department of Physiology, College of Medicine, Korea University, Anam-dong 5-ga, Seongbuk-gu, Seoul 02842, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Glenn F. King
Received: 2 December 2015 / Revised: 14 January 2016 / Accepted: 18 January 2016 / Published: 22 January 2016
(This article belongs to the Special Issue Arthropod Venoms)
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Abstract

Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain. View Full-Text
Keywords: bee venom acupuncture; chemotherapy induced neuropathic pain; morphine; oxaliplatin bee venom acupuncture; chemotherapy induced neuropathic pain; morphine; oxaliplatin
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Kim, W.; Kim, M.J.; Go, D.; Min, B.-I.; Na, H.S.; Kim, S.K. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. Toxins 2016, 8, 33.

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