Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats

作者：Juan Niu, Dujuan Huang, Rui Zhou, Ming-Xia Yue, Tao Xu, Junna Yang, He Li, Hong Tian, Xiaohong Liu, Junwei Zeng · 发表于：Journal of Neuroinflammation · 年份：2017 · DOI：10.1186/s12974-017-0960-0 · 被引用次数：75 · 研究领域：Pain Mechanisms and Treatments、Cannabis and Cannabinoid Research、Nerve injury and regeneration

More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y 12 and P2Y 13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y 12 and P2Y 13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain. The paw withdrawal latency (PWL) was used to evaluate thermal hyperalgesia in neuropathic rats. The expression of P2Y 12 and P2Y 13 receptors, p-p38MAPK, and NF-kappaBp65 was detected with RT-PCR and western blotting analysis. Treatment with AM1241 produces a pronounced inhibition of CCI-induced thermal hyperalgesia and significantly inhibited the increased expression of P2Y 12 and P2Y 13 receptors at the mRNA and protein levels, which open up the possibility that P2Y 12 and P2Y 13 receptor expression are downregulated by CB2 receptor agonist AM1241 in CCI rats. Western blot analysis demonstrated that AM1241 reduced the elevated expression of p-p38MAPK and NF-κBp65 in the dorsal spinal cord induced by CCI. After administration with either SB203580 (p38MAPK inhibitor) or PDTC (NF-kappaB inhibitor), the levels of P2Y 13 receptor expression in the dorsal spinal cord were lower than those in the CCI g...