内源性大麻素通（ECBs）通过对星形胶质细胞（AST）功能的调节参与镇痛效应，但相关分子机制尚不清楚。据文献报道及我们前期研究，推测ECBs的镇痛效应可能通过相应受体干扰AST内MAPK-谷氨酸-谷氨酰胺循环通路实现。通过离体实验，观察siRNA沉默或特异性抑制剂阻断大麻素受体或MAPK途径后，对ECBs效应的影响和对下游谷氨酸-谷氨酰胺循环的调节作用，明确起主导作用受体亚型和具体MAPK途径，分析RNA干扰瞬时效应，阐述通路调控机制。通过行为学、形态学和核磁功能成像（BOLD-fMRI）,观察炎性痛和神经病理痛两种情况下，ECBs镇痛效应是否存在不同的大麻素受体亚型和MAPK途径调节机制；在疼痛不同阶段，观察受体亚型表达是否存在差异及重新分布，MAPK途径是否存在并行表达；建立大鼠BOLD-fMRI影像与解剖对应关系。研究结果旨在阐明内源性大麻素痛调制机制，为临床治疗提供理论依据和新思路

Endocannabinoid（ECBs）involves in the analgesic effect through regulating the function of astrocytes, however, the molecular mechanism is still unclear. Based on literatures and our previous study results, we propose that the analgesic effect of ECBs is achieved by interfering the astrocyte MAPK-glutamate-glutamine pathway via corresponding receptors. In this study, we aim to investigate the influence on ECBs effect and the modulation of downstream glutamate-glutamine cycle after inhibition of cannabinoid receptor or MAPK pathway by siRNA or specific antagonist, which will clarify the major receptor subunit and specific MAPK pathway and will be helpful to analyze the transient effect of RNA intervene and to elucidate the mechanism of modulation pathway. Through behavioral test, morphological study and BOLD-fMRI (blood oxygen level dependent functional magnetic resonance imaging) scanning, we will investigate whether there are different cannabinoid receptor subunits and MAPK pathways in inflammatory and neuropathic pains. Moreover, subunits re-distribution and synergistic effects of MAPK pathways will be investigated if there is expression change, and the corresponding relationship between rat BOLD-fMRI and anatomy will be further established and confirmed. This study will enrich the pain modulation theory of endocannabinoid and may provide theoretic support and new potential target for treatment of pain.