B Vitamins Potentiate Acute Morphine Antinociception and Attenuate the Development of Tolerance to Chronic Morphine in Mice
B Vitamins Potentiate Acute Morphine Antinociception and Attenuate the Development of Tolerance to Chronic Morphine in Mice
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B 族维生素可增强小鼠急性吗啡镇痛作用并减弱慢性吗啡耐受性的发展
DOI：
10.1093/pm/pnw358
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发表时间：
2017-10-01
期刊：
影响因子：
3.1
通讯作者：
Song, Xue-Jun
中科院分区：
文献类型：
--
作者：
Deng, Xue-Ting;Han, Yuan;Song, Xue-Jun
阿片类镇痛药是治疗严重疼痛最有效的药物，但其临床应用往往受到镇痛耐受性发展的阻碍。吗啡的作用和神经性疼痛之间有惊人的相似之处。我们已经证明，B族维生素可以减轻周围神经损伤、感觉神经元炎症/压迫和短暂脊髓缺血后的神经性疼痛。鉴于这种相似性，本研究探讨了B族维生素是否能够改变小鼠吗啡的抗伤害效应以及吗啡耐受。使用甩尾在ICR小鼠中评估抗伤害感受。本实验观察了B族维生素对吗啡急性镇痛和慢性吗啡耐受的影响：（1）B族维生素与吗啡合用可增强吗啡急性镇痛作用。2)B族维生素减弱慢性吗啡给药的抗伤害性耐受的发展，并抑制吗啡诱导的脊髓中的p-NR 1、p-PKC。3)吗啡诱导小胶质细胞活化，如脊髓中p38 MAPK磷酸化、IBA 1和IL-1 β增加所证明的，并且这些变化被B族维生素抑制。4)B族维生素单独给药对痛阈和小胶质细胞活性无明显影响，B族维生素可增强吗啡的急性镇痛作用，减弱慢性吗啡耐受。
Opiate analgesics are the most effective treatments for severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. There are striking similarities between morphine actions and neuropathic pain. We have demonstrated that B vitamins can attenuate neuropathic pain after peripheral nerve injury, sensory neuron inflammation/compression, and transient spinal cord ischemia. Given this similarity, the present study investigated whether B vitamins might be able to modify the antinociceptive effect of morphine as well as morphine tolerance in mice.Cell signaling was assayed by Western blot and immunohistochemistry. Antinociception was assessed in ICR mice using the tail flick. The effects of B vitamins on acute morphine-induced antinociception and chronic morphine tolerance were studied.1) Co-administration of B vitamins with morphine potentiates acute morphine antinociception. 2) B vitamins attenuate the development of antinociceptive tolerance to chronic morphine administration and inhibit morphine-induced p-NR1, p-PKC in the spinal cord. 3) Morphine induces microglial activation, as evidenced by increased p38 MAPK phosphorylation, IBA1, and IL-1 beta in the spinal cord, and these changes are inhibited by B vitamins. 4) Treatment of B vitamins alone shows no notable effects on pain threshold and activity of microglia invivo.B vitamins potentiate acute morphine antinociception and attenuate chronic morphine tolerance.