PMID- 29313211 OWN - NLM STAT- MEDLINE DCOM- 20180830 LR - 20210109 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 43 IP - 3 DP - 2018 Mar TI - Up-Regulation of CX3CL1 via STAT3 Contributes to SMIR-Induced Chronic Postsurgical Pain. PG - 556-565 LID - 10.1007/s11064-017-2449-8 [doi] AB - Chronic postsurgical pain (CPSP) often occurs after surgery and has a strong impact on patients' daily lives. However, the underlying mechanism of CPSP remains unknown. Here, we used a skin/muscle incision and retraction (SMIR) model to investigate the role of CX3CL1 in SMIR-induced pain and its underlying mechanism. We found that up-regulation of CX3CL1 in the spinal dorsal horn contributed to SMIR-induced mechanical allodynia. The use of a CX3CL1-neutralizing antibody to block CX3CL1 attenuated mechanical allodynia induced by SMIR surgery. We also found that phospho-STAT3 co-localizes with CX3CL1 in spinal neurons after SMIR surgery and that this contributes to SMIR-induced mechanical allodynia. Intrathecal administration of the STAT3 inhibitor S3I-201 suppressed up-regulation of CX3CL1 at both the protein and mRNA levels after SMIR surgery. Chromatin immunoprecipitation further demonstrated that SMIR promotes the recruitment of STAT3 to the cx3cl1 gene promoter (- 1032/- 1022). These findings suggest that activation of STAT3 after SMIR mediates the up-regulation of CX3CL1, leading to mechanical allodynia, and that this upregulation may partly be due to the enhanced recruitment of STAT3 to the cx3cl1 gene promoter after SMIR. FAU - Shen, Yijia AU - Shen Y AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Li, Dai AU - Li D AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Li, Bo AU - Li B AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Xi, Peng AU - Xi P AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Zhang, Yun AU - Zhang Y AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Jiang, Youshui AU - Jiang Y AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Xu, Yehao AU - Xu Y AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. FAU - Chen, Hui AU - Chen H AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. chenhui_md@163.com. FAU - Xiong, Yuanchang AU - Xiong Y AD - Department of Anesthesiology, The First Affiliated Hospital of the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. proychxiong@163.com. LA - eng GR - 81600955/National Natural Science Foundation of China/ GR - 17ZR1438200/Natural Science Foundation of Shanghai/ PT - Journal Article DEP - 20180108 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Chemokine CX3CL1) RN - 0 (Cx3cl1 protein, rat) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, rat) SB - IM MH - Animals MH - Chemokine CX3CL1/*metabolism MH - Chronic Pain/*metabolism MH - Disease Models, Animal MH - Hyperalgesia/metabolism MH - Male MH - Muscles/surgery MH - Pain Measurement/methods MH - Pain, Postoperative/*metabolism MH - Rats, Sprague-Dawley MH - STAT3 Transcription Factor/*metabolism MH - Skin/injuries MH - Transcriptional Activation/physiology MH - *Up-Regulation OTO - NOTNLM OT - CX3CL1 OT - Chronic postsurgical pain OT - P-STAT3 OT - Skin/muscle incision and retraction EDAT- 2018/01/10 06:00 MHDA- 2018/08/31 06:00 CRDT- 2018/01/10 06:00 PHST- 2017/09/11 00:00 [received] PHST- 2017/12/05 00:00 [accepted] PHST- 2017/11/29 00:00 [revised] PHST- 2018/01/10 06:00 [pubmed] PHST- 2018/08/31 06:00 [medline] PHST- 2018/01/10 06:00 [entrez] AID - 10.1007/s11064-017-2449-8 [pii] AID - 10.1007/s11064-017-2449-8 [doi] PST - ppublish SO - Neurochem Res. 2018 Mar;43(3):556-565. doi: 10.1007/s11064-017-2449-8. Epub 2018 Jan 8.