The Impact Of Chronic Psychological Stress And Chronic Pain Stress On Immune Function In Rats

Objectives: Chronic psychological stress and chronic pain stress as familiar types of stress are endangering health of human.The immune system is one of the most important injury mechanisms of chronic stress.At present the argument about the effects of chronic psychological stress and chronic pain stress on the immune function is going on.Some researchers believe that chronic stress suppress the immunity,while some studies have shown that chronic stress have diverse effects on different parts of immune system.In addition,different types of chronic stress have different effects on the immune system.Thus,what effects do the different types of chronic stress have on the immune system? According to establish the chronic psychological stress and chronic pain stress models in rats,we studied the changes of immune function in chronic psychological stress and chronic pain stress in rats and explored the immune mechanism of chronic psychological stress and chronic pain stress.Methods: Male Sprague-Dawley rats were randomly divided into three groups,including the control group,the chronic stress group and the chronic pain group.The chronic unpredictable mild stress model was established by randomly presenting 7 stimuli in 35 days.By injecting Complete Freund’s adjuvant,the chronic inflammatory pain model was established.The chronic stress group and the chronic pain group were subjected to behavioral tests,including open field test and sugar preference test.The anxiety-like behaviors and depression-like emotion of the rats were examined.The paw withdrawal mechanical threshold of the chronic pain group and the control group were examined.The proportion of peripheral blood immune cells,includingCD3+ CD8+ T cells,Th1 cells,Th2 cells,Th17 cells,Treg cells,B-2 cells,and the ratio of Th1 cells/Th2 cells and Th17 cells/Treg cells were detected by flow cytometry.The concentration of serum corticosterone was measured by ELISA kit.The concentration of serum IL-1,IL-1β,IL-2,IL-4,IL-6,IL-10,IL-13,IFN-γ and TNF-α were measured by cytokine array technology.Results: In this study we concluded that(1)Chronic psychological stress induced anxiety-like behavior and depression-like emotions in rats.In the open field test,the travel distance,the central crossing frequency and the number of rearing in the chronic stress group were also significantly reduced.In the sucrose preference test,the post-testing of sucrose preference% was significantly lower than that in the pre-testing.Chronic psychological stress and chronic pain stress all induced decrease of concentration of serum corticosterone.(2)Chronic pain stress induced hyperalgesia in rats.In the pain threshold test,the paw withdrawal mechanical threshold of the chronic pain stress was significantly decreased in the chronic pain group.(3)Chronic psychological stress and chronic pain stress both caused imbalance of Th1/Th2 ratio in peripheral blood.Through the flow cytometry,we found that Th2 cells in chronic stress group were significantly raised and Th1 cells in chronic pain group were reduced.The Th1/Th2 ratios in chronic stress group and chronic pain group were significantly decreased.(4)Chronic psychological stress and chronic pain stress both induced the changes of serum pro-inflammatory cytokines expression.The concentrations of serum IL-1α,IL-1β and IFN-γ in chronic stress group were significantly decreased.The concentration of serum TNF-α in the chronic pain group was significantly elevated.The concentration of serum IL-2 was significantly elevated in both chronic stress group and chronic pain group.Conclusions:(1)Different effects of chronic psychological stress and chronic pain stress on immune indexes showed that stress is a specific change,which partly questioned Selye’s theories about non-specificity of stress.(2)Due to chronic pain stress,Th1/Th2 balance in rats was destroyed,and serum concentration of TNF-α was significantly increased.These indexes could mediate chronic pain stress inducing autoimmune diseases,cancer and virus infection.(3)Chronic psychological stress led to a significant rise in ratio of Th2 cells of rats and Th1/Th2 imbalance,which suggested that chronic psychological stress mainly influence the humoral immune function.(4)Caused by chronic psychological stress,concentration of serum IFN-γ,IL-1α,IL-1β dropped significantly,which could be one of the mechanisms of chronic psychological stress inducing infection disease.These indexes could be used as a biological marker of human chronic stress damage.