title: Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.
abstract: A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. leedongxing@naver.com.
authors.forename: Dongxing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. eyounju@naver.com.
authors.forename: Younju
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. thasnow@gmail.com.
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Herbology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. niceday@khu.ac.kr.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. hbae@khu.ac.kr.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. skkim77@khu.ac.kr.|Department of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, Korea. skkim77@khu.ac.kr.
authors.forename: Sun Kwang
authors.initials: SK
authors.lastname: Kim
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001514:Bee Venoms / Q000737:chemistry* / Q000201:enzymology; D001522:Behavior, Animal / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D054467:Phospholipases A2 / Q000302:isolation & purification / Q000627:therapeutic use*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D000970:Antineoplastic Agents; D001514:Bee Venoms; D009944:Organoplatinum Compounds; D018341:Receptors, Adrenergic, alpha-2; D000077150:Oxaliplatin; D054467:Phospholipases A2
keywords: Bee Venom; neuropathic pain; noradrenergic; oxaliplatin; phospholipase A2