Effects Of Chronic Psychological Stress And Chronic Pain On Neurotransmitters And Endocrine Gland Axes In Rats

Objectives: Chronic psychological stress and chronic physical pain are important stressors which can cause serious damage to people's health and quality of life.In recent years,more and more studies have found the co-morbidity phenomenon of physical and mental problems caused by chronic psychological stress and chronic pain,but the codisease mechanism is still unclear.Therefore,we conducted a study on chronic psychological stress and pain stress on neurotransmitters and endocrine glands in rats in order to find some mechanisms of the action.Methods: Male Sprague-Dawley rats were randomly divided into control group,chronic stress group and chronic pain group.Psychological stress group and pain group were established 35 days chronic unpredictable mild stress model and chronic inflammatory pain model.Before and after the model establishment,all rats were subjected to sucrose preference and open field behavior test.At the same time,the rats in the pain group and the saline control group were detected the mechanical hyperalgesia every other week.The levels of 5-HT(Serotonin),NE(Noradrenaline),DA(Dopamine),Glu(Glutamate)and GABA(Gamma aminobutyric acid)in the hypothalamus of rats were measured by high-performance liquid-phase fluorescence method.The blood samples were taken from the heart and detected by enzyme-linked immunosorbent assay.The levels of CRH(Corticotropin releasing hormone),ACTH(Adrenocorticotrophic hormone),CORT(Corticosterone)in the HPA(Hypothalamic pituitary adrenal)axis,TRH(Thyrotropin-releasing hormone),TSH(Thyroidstimulating hormone),T3(Triiodothyronine),T4(Tetraiodothyronine)in the HPT(Hypothalamic-pituitary-thyroid)axis and GnRH(Gonadotropin releasing hormone),LH(Luteinizing hormone),T(Testosterone)in the HPG(Hypothalamic-pituitarygonadal)axis were measured.Results:(1)Compared with the control group,the sucrose preference was significantly decreased in the chronic psychological stress group,whose total distance,the number of standing and central crossing frequency were significantly reduced in the open field.Rats in the chronic psychological group showed apparent anxiety-and depression-like behavior;(2)The mechanical pain threshold of rats in the chronic pain stress group was significantly reduced,which indicated the induction of pain sensitization;(3)The relative levels of NE,Glu and GABA in the hypothalamus of rats of both stressed groups were significantly increased,but the 5-HT and DA did not change significantly;(4)Chronic psychological stress significantly reduced the effect of HPA on CORT and the secretion of TSH on HPT axis,and there was no significant change in other hormone indexes;(5)Chronic pain significantly increased the release of TRH in rat HPT axis,but TSH concentration in serum was significantly reduced,while other hormonal indicators had not been significantly affected;(6)Neither types of stress were significantly affected on the rat HPG axis hormone secretion.Conclusions:(1)The dysregulation of NE,Glu and GABA in the hypothalamus could be an important mechanism of chronic psychological stress induced anxiety-and depression-like behavior and painful sensitization in rats.Meanwhile,the abnormalities of NE,Glu and GABA might be causes of comorbidity of depression with chronic pain;(2)The dysfunction of HPA axis and HPT axis could be involved in the process of chronic stress of impaired immunity,cognitive and emotional abilitythrough the impact of the nervous system and endocrine system function;(3)The results showed that the HPT axis might be one of the important mechanisms of chronic pain stress leading to sensory sensitization.It could be used as a biological index for the study of chronic pain disorders in the human body;(4)There is no clear evidence that the HPG axis is involved in the process of chronic stress on depression-like behavior in this study,suggesting that the HPG axis may not be a mechanism of chronic stress induced depression-like behavior;(5)The effects of chronic psychological stress and chronic pain on HPA and HPT axes showed that the rats could specifically respond to different stress which is not consistent with Selye's opinion that claimed stress is a non-specific syndrome generated by the body to external stimuli.