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Background:Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa).The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 (125I) seed implantation.Methods:The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125I seeds CLDR irradiation.The orthotopic models of PNI were established,and 125I seeds were implanted in tumor.The PNI-related molecules were analyzed.In 30 patients with panCa,the pain relief was assessed using a visual analog scale (VAS).Pain intensity was measured before and 1 week,2 weeks,and 1,3,and 6 months after 125I seed implantation.Results:The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites.In co-culture groups,the increased number of DRG neurites and pancreatic cells in radiation group was significantly less.In orthotopic models,the PNI-positive rate in radiation and control group was 3/11 and 7/11;meanwhile,the degrees of PNI between radiation and control groups was significant difference (P ＜ 0.05).At week 2,the mean VAS pain score in patients decreased by 50％ and significantly improved than the score at baseline (P ＜ 0.05).The pain scores were lower in all patients,and the pain-relieving effect was retained about 3 months.Conclusions:The CLDR irradiation could inhibit PNI of PanCa with the value of further study.The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.