Study On Central Sensitization Mechanism Of Pain Induced By Th1 And Th17 Cell Infiltration In L5-S2 Spinal Cord Of CP/CPPS Rats

Research Background and Objective:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)has a long period of chronic pain and poor treatment effect,which seriously affects the physical and mental health of patients.The autoimmune dysregulation of CP/CPPS has become a research hotspot this year.Th1 and Th17 cells are believed to be related to CP/CPPS pain,and central sensitization is also considered to be one of the important factors of chronic pain.Based on the neural regulation mechanism of CP/CPPS pain,this study confirmed L5-S2 spinal infiltration of CD4~+T cell subsets and their involvement in central sensitization mechanism in CP/CPPS rat model,and tried to find a new way of thinking about the pathogenesis of CP/CPPS pain.Materials and Methods:3-4 weeks,weight 250-350-g 40 adult male SPF SD rats randomly divided into control group and CP/CPPS model group,through the prostate gland in situ injection of complete freund’s adjuvant and the same amount of saline constructing model,Von Frey pain test and HE staining were used to observe the inflammatory infiltration in the prostate tissue of the two groups after 4 weeks.Flow cytometry,real-time quantitative PCR(RT-q PCR),immunofluorescence detection and other methods were used to analyze the infiltration of CD4~+T cell subsets L5-S2 in the spinal cord.The expression levels of GFAP,CR3 and inflammatory cytokines in spinal cord were detected to explore the central sensitization mechanism of Th1 and Th17 cells to CP/CPPS pain in rats.Results:1、There was infiltration of peripheral T cells in L5-S2 spinal cord tissue in CP/CPSS rat pain model,and the specific cell subtypes were Th1 cells and Th17 cells.The expressions of specific cytokines INF-γ,IL-17 and RORγt in both cells were up-regulated.2、Th1 and Th17 cells activate glial cells to promote the m RNA expression of chemokines(CCL2,CCL20,CXCL10)and pro-inflammatory factors(IL-1β,TNF-α,IL-6),and induce the central sensitization process.Conclusion:In conclusion,our work identified the specific subsets of CD4~+T cells infiltrating in L5-S2 spinal cord neurons of CP/CPPS model rats as Th1 and Th17 cells.They secrete inflammatory cytokines such as IFN-γand IL-17 to injure neuronal cells and affect nerve conduction,promote central sensitization and activate astrocytes and microglia,resulting in increased secretion of inflammatory cytokines such as IL-1β,TNF-αand IL-6,and chemokines such as CCL2,CCL20 and CXCL10.Meanwhile,chemokines can provide favorable conditions for Th1 cells and Th17 cells to infiltrate the spinal cord tissue.Under the interaction between immune cells and glial cells,the excitability of synaptic transmission is enhanced and central sensitization occurs,leading to the occurrence and development of pain.