Selective suppression of microglial activation by paeoniflorin attenuates morphine tolerance

作者：Chun‐Yi Jiang, Long Xu, L. Chen, Y. Han, Jinrong Tang, Y. Yang, G. Zhang, W. Liu · 发表于：European Journal of Pain · 年份：2014 · DOI：10.1002/ejp.617 · 被引用次数：39 · 研究领域：Pain Mechanisms and Treatments、Neuropeptides and Animal Physiology、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: The development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord play a critical role in morphine tolerance. The present study investigated the effects and possible mechanisms of a natural compound, paeoniflorin, in morphine tolerance via its specific inhibition of microglial activation. METHODS: The microglia cell line BV-2 was used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signalling was assayed by Western blot and immunohistochemistry. Nociception was assessed in Sprague-Dawley rats and CD-1 mice using Hargreaves' methods or the hot-plate test, respectively. RESULTS: (1) Morphine induces robust BV-2 cell activation, as evidenced by increased p38 mitogen-activated protein kinase (MAPK) phosphorylation, nuclear factor (NF)-κB translocation and proinflammatory cytokine expression. These changes are inhibited by paeoniflorin. (2) Co-administration of paeoniflorin with morphine potentiates morphine antinociception by inhibiting p38 MAPK/NF-κB signalling in the spinal cord. (3) Co-administration of paeoniflorin suppresses morphine-increased expression of toll-like receptor-4 both in BV-2 cells and within the spinal cord following chronic morphine treatment. CONCLUSION: Paeoniflorin directly suppresses morphine-induced microglial activation and thus results in potentiation of...