Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice
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 diff...
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MDPI AG
2016-01-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/2/33 |
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| author | Woojin Kim Min Joon Kim Donghyun Go Byung-Il Min Heung Sik Na Sun Kwang Kim |
| author_facet | Woojin Kim Min Joon Kim Donghyun Go Byung-Il Min Heung Sik Na Sun Kwang Kim |
| author_sort | Woojin Kim |
| collection | DOAJ |
| description | 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. |
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| last_indexed | 2024-04-14T00:30:07Z |
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| spelling | doaj.art-493e694e6e694da89c316dcdd3e127722022-12-22T02:22:34ZengMDPI AGToxins2072-66512016-01-01823310.3390/toxins8020033toxins8020033Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in MiceWoojin Kim0Min Joon Kim1Donghyun Go2Byung-Il Min3Heung Sik Na4Sun Kwang Kim5Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, KoreaDepartment of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, KoreaDepartment of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, KoreaYeongju Municipal Hospital, 697 Jangan-ro, Anjeong-myeon, Gyeongsangbuk-do, Yeongju-si 36051, KoreaDepartment of Physiology, College of Medicine, Korea University, Anam-dong 5-ga, Seongbuk-gu, Seoul 02842, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, KoreaOxaliplatin, 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.http://www.mdpi.com/2072-6651/8/2/33bee venom acupuncturechemotherapy induced neuropathic painmorphineoxaliplatin |
| spellingShingle | Woojin Kim Min Joon Kim Donghyun Go Byung-Il Min Heung Sik Na Sun Kwang Kim Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice Toxins bee venom acupuncture chemotherapy induced neuropathic pain morphine oxaliplatin |
| title | Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice |
| title_full | Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice |
| title_fullStr | Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice |
| title_full_unstemmed | Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice |
| title_short | Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice |
| title_sort | combined effects of bee venom acupuncture and morphine on oxaliplatin induced neuropathic pain in mice |
| topic | bee venom acupuncture chemotherapy induced neuropathic pain morphine oxaliplatin |
| url | http://www.mdpi.com/2072-6651/8/2/33 |
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