Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.
Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.
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DOI：
10.3390/toxins7072422
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发表时间：
2015-06-29
期刊：
影响因子：
4.2
通讯作者：
Kim SK
中科院分区：
文献类型：
--
作者：
Li D;Lee Y;Kim W;Lee K;Bae H;Kim SK
广泛用于治疗转移性结直肠癌的奥沙利铂单次输注可诱导特定感觉神经毒性体征，当暴露于冷或机械刺激时会触发或加重。蜂毒（BV）在韩国传统上用于治疗各种疼痛症状。我们最近的研究表明，BV通过去甲肾上腺素能和肾上腺素能镇痛通路减轻奥沙利铂诱导的大鼠冷异常性疼痛。在本研究中，我们进一步研究了BV衍生的磷脂酶A2（bvPLA 2）是否减轻奥沙利铂诱导的小鼠冷和机械异常性疼痛及其机制。分别通过丙酮和后爪上的von Frey毛发试验评价冷和机械异常性疼痛的行为体征。在奥沙利铂注射（6 mg/kg，i. p.）后1天观察到显著的异常性疼痛体征。每日施用bvPLA 2（0.2mg/kg，i. p.）连续5天显著减弱冷和机械异常性疼痛，这比BV（1 mg/kg，i. p.）的作用更有效。通过注射N-（2-氯乙基）-N-乙基-2-溴苄胺盐酸盐（DSP 4，50 mg/kg，i. p.）阻断bvPLA 2的镇痛作用，而通过注射DL-对氯苯丙氨酸（PCPA，150 mg/kg，i. p.）连续三天没有。此外，咪唑克生（α2-肾上腺素能受体拮抗剂，1 mg/kg，i. p.）完全阻断bvPLA 2诱导的抗痛觉超敏作用，而哌唑嗪（α1-肾上腺素能拮抗剂，10 mg/kg，i. p.）没有。这些结果表明，bvPLA 2治疗通过α2肾上腺素能受体激活去甲肾上腺素能系统，但不通过肾上腺素能系统，强烈抑制奥沙利铂诱导的小鼠急性寒冷和机械性异常性疼痛。
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.