化疗药引起的慢性疼痛限制其临床应用，机制不清，我们已经发现STAT3激活后通过上调CXCL12介导慢性疼痛。circRNA能通过结合蛋白质、吸附miRNA等机制参与神经系统疾病。我们预实验发现：抗微管化疗药引起的慢性疼痛显著上调circ_chr10，给予circ_chr10 shRNA可抑制STAT3激活和CXCL12蛋白上调，缓解了慢性疼痛；同时预测发现circ_chr10与CXCL12的miR-598存在结合位点，而miR-598mimic能抑制CXCL12表达。以上结果提示：circ_chr10可能通过激活STAT3或吸附CXCL12相关的miRNA介导CXCL12的上调参与慢性疼痛。本项目拟解决1）circ_chr10通过何种机制激活STAT3介导CXCL12上调；2）circ_chr10与miRNA相互作用介导CXCL12上调的机制。本研究将为化疗药导致的慢性疼痛提供新的治疗靶点

Mechanism of chronic pain induced by chemotherapeutic agents is not clear totally. We have found that CXCL12 expression via STAT3 activation was very important in chronic pain. Circular RNA (circRNA) exerts its biological function by binding protein and miRNA sponge in the disease process of nervous system. Our preliminary evidence was shown that expression of circ_chr10 was significantly upregulated in the rat spinal cord after anti-microtubule chemotherapeutic agents injected. Intrathecal injection of circ_chr10 shRNA significantly attenuated the hypersensitivity induced by anti-microtubule chemotherapeutic agents by inhibiting the STAT3 activation and CXCL12 expression. Furthermore, bioinformatics analysis showed that there were several binding sites between circ_chr10 and CXCL12 miRNA, such as miR-598, which its mimic could inhibit the expression of CXCL12. Taken together, circ_chr10 might regulate the chronic pain process via activating STAT3 or miRNA sponge function. The presents study is going to discuss the mechanism that circ_chr10 promotes the expression of CXCL12 via STAT3 phosphorylation and the sponge effects of miRNA under the process of chronic pain induced by anti-microtubule chemotherapeutic agents. Our research will provide novel target for chronic pain induced by of anti-microtubule chemotherapeutic agents.