title: Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.
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.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. thasnow@gmail.com.|Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. thasnow@gmail.com.
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. junesnest@naver.com.
authors.forename: Min Joon
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. drum2r@daum.net.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Go
authors.affiliation: Yeongju Municipal Hospital, 697 Jangan-ro, Anjeong-myeon, Gyeongsangbuk-do, Yeongju-si 36051, Korea. mbi@khu.ac.kr.
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Min
authors.affiliation: Department of Physiology, College of Medicine, Korea University, Anam-dong 5-ga, Seongbuk-gu, Seoul 02842, Korea. hsna@korea.ac.kr.
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. skkim77@khu.ac.kr.|Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 02447, Korea. skkim77@khu.ac.kr.
authors.forename: Sun Kwang
authors.initials: SK
authors.lastname: Kim
mesh_terms: D026881:Acupuncture; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001514:Bee Venoms / Q000627:therapeutic use*; D003080:Cold Temperature; D003131:Combined Modality Therapy; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D010812:Physical Stimulation; D011957:Receptors, Opioid / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000970:Antineoplastic Agents; D001514:Bee Venoms; D009292:Narcotic Antagonists; D009944:Organoplatinum Compounds; D011957:Receptors, Opioid; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D014326:Tropanes; D000077150:Oxaliplatin; D009270:Naloxone; D009020:Morphine; C042253:bemesetron
keywords: bee venom acupuncture; chemotherapy induced neuropathic pain; morphine; oxaliplatin