Abstract: Objective To explore the mechanism of the affection of miR-16 on 5HT reuptake in the neuropathtic pain by studying the miR-16 regulating SERT expression. Methods Forty adult male SD rats were randomly divided into control group (C group),sham operation group (S group),chronic constriction injury group (CCI group),chronic constriction injury plus fluoxetine group (CCI/F group),10 rats per group.Left sciatic nerve of rats in CCI group were freed and loosely compressed by sutures,while rats in the S group were only freed the neurilemma.The mechanism withdraw threshold (MWT) was test in the preoperative day and the day 1,3,5,7,14 after surgery.Fourteen days after surgery,the rats were sacrificed,and the rapheal nuclei of brain stem were taken.The miR16 expression was tested by qRT-PCR,and SERT was tested by western blot.The 5HT level in the tissue homogenate was analyzed by ELISA assay. Results Compared with the S group,the MWT in the CCI group was significantly declined in the first day after surgery (t=5.167,P<0.001),but the value was increased in the CCI/F group (t=28.640,P<0.001).SERT in the rapheal nuclei of CCI group was increased but decreased in the CCI/F group as shown by western blot.Compared with the S group,5HT in the rapheal nuclei of CCI group was significantly decreased (t=17.92,P<0.001),but increased in the CCI/F group (t=7.232,P=0.002). Conclusion miR-16 can regulate the expression of SERT in the rapheal nuclei,thereby affect the reuptake of 5HT to influence the neuropathic pain.