背根神经节(DRG)神经元的过度激活与骨癌痛的发生和维持密切相关，而PAR-2/TRPV-1通路可调控DRG神经元兴奋性，进而干预早期急性骨癌痛的进展。我们的前期研究结果显示，基于化瘀通络、解毒抗癌法的消癥止痛外用方能快速控制早期急性骨癌痛，其止痛机制与促使脊髓内c-fos蛋白表达下调有关，而c-fos是PAR-2调控的重要下游蛋白，且该方中主要药物可抑制DRG神经元上的TRPV-1受体。因此，我们推测消癥止痛外用方可能是通过调控DRG神经元上PAR-2/TRPV-1通路，达到缓解并治疗骨癌痛的作用。通过建立大鼠骨癌痛及体外癌与DRG神经元非接触共培养的细胞模型，我们拟从疼痛行为学、影像学及分子生物学等不同层次揭示消癥止痛外用方治疗骨癌痛的作用及分子机制。我们的结果可能为化瘀通络、解毒抗癌法外用治疗骨癌痛提供科学依据，也可为临床上寻找抗骨癌痛新的治疗方法和新的药物靶点提供新的思路。

Excessive activation of dorsal root ganglion (DRG) neurons is crucial for the development of bone cancer pain, and the PAR-2/TRPV-1 pathway regulates the excitability of DRG neurons and early acute bone cancer pain. Our previous studies have shown Xiaozhen Zhitong Paste we generated based on regulating "circulation network" and detoxification relieve early acute bone cancer pain in patients.It's mechanism of relieving pain is because of down-regulation of c-fos protein in spinal cord, and most of the prescription drugs can inhibit TRPV-1 receptor in DRG neurons. Accoridngly, we hypothesize that the therapeutic effect of Xiaozhen Zhitong Paste may regulate the PAR-2/TRPV-1 signal pathway, leading to relief of bone cancer pain. We will employ rat model of bone cancer pain and in vitro non-contact cacner cells and DRG neuron coculture system to reveal molecualr mechanisms underlying the anti-pain therapeutic effect of Xiaozhen Zhitong Paste using pain measurement, imaging analysis system and molecular biology. Potentially, our findings may probide new scientific basis for understanding the role of regulating "circulation network" and detoxification-based traditional medicines for the treatment of bone cancer pain. Our findings may also reveal new therapuetic targets and aid in the design of new therapies for the intervention of bone cancer pain in humans.