Correlations Between Endogenous Npy And Pain,Anxiety And Depression In Patients With Endometriosis

Endometriosis(EMs)occurs in approximately 10-15% of women of reproductive age,which aetiology is unknown now but relapse easily.The typical symptoms of EMs include pain of the various forms,however the mechanism of pain is still unclear now,which includes severe periodic non-strand pelvic pain during menstruation,strangulated pelvic pain throughout the menstrual cycle,deep intercourse pain and pain of bowel movements.It is still difficult to solve the pain by surgery and drugs thoroughly,however most patients are accompanied by psychological disorders such as anxiety and/or depression,which ultimately aggravates the symptom and leads to treat it more difficultly.It is urgent to explore drugs to relieve pain,anxiety and depression in patients with endometriosis simultaneously.The growth of endometriotic lesions is related with innervation and vascular supply,and endometriosis pain mechanism is closely related to neurotransmitters.In recent years,the close relationship between peptide neurotransmitters and pain mechanisms has attracted some researchers.Neuropeptide Y(NPY)is one of the most important peptide neurotransmitters in human body,which is an vasoactive substance in the endocrine of the nervous system,and has neurotransmitter and vasoregulatory effects and is widely distributed in tissues,internal organs and glands,and has strong vasoconstrictor activity.In recent years,it has been found that NPY and its receptors play an important role in the neuropathic pain mechanism,confirmed that exogenous NPY plays analgesic and/or painful effect through it's receptors Y1 and Y2,respectively.Then we speculate that NPY would participate in the pain mechanism of endometriosis.Some researchers also found that NPY and its receptors Y1 and Y2 have important changes in the brain midbrain,amygdala and hippocampus of patients with endometriosis pain,which play key roles in pain,anxiety,and depression.We speculate that the expression of endogenous NPY and its receptors Y1,Y2 would affect the pain of endometriosis,and participate in the mental disorders like anxietyand depression caused by pain.In order to confirm the above speculation,we have explored the following three parts:Firstly,we detected the distribution and expression of endogenous NPY and its receptors Y1 and Y2 in ectopic and eutopic of patients with endometriosis pain and normal endometrium,and have explored the correlation between endometriosis pain and endogenous NPY and its receptors Y1,Y2 whose situation and expression in different pain degrees and it's possible mechanisms.Secondly,several questionnaires have been completed in patients with endometriosis pain,which analysis of the relationship between anxiety,depression and endometriosis pain,so that we could valuate satisfaction with sexual function and the quality of life related to endometriosis pain,anxiety,depression degree.Thirdly,according to the results of the questionnaire,we have explored the correlation between serum NPY expression and pain,anxiety,depression degree.Part I Discuss the Relationship between Endogenous NPY and its Receptors Y1,Y2 and Endometriosis Pain Purpose:To detect the distribution and expression of endogenous NPY and its receptors Y1 and Y2 in ectopic,eutopic and normal endometrium,and to explore correlation between NPY and its receptors Y1,Y2 and the degree of endometriosis pain.Methods:1)69 hospitalized patients' ectopic and eutopic endometrium were collected,who were diagnosed endometriosis by pathology after open or laparoscopic surgery,and we collected normal endometrium from 60 patients as the control group.According to the different Visual analogue scale(VAS)scores,patients with endometriosis were divided into four subgroups: 22 in the painless group,20 in the mild pain group,15 in the moderate pain group,and 12 in the severe pain group.2)Immunohistochemistry,Western Blot,Real-time PCR were used to detect the distribution and expression of endogenous NPY and its receptors Y1 and Y2 in ectopic,eutopic and normal endometrial paraffin sections,and in foursubgroups respectively.Results:1)Immunohistochemistry results showed that NPY was expressed in ectopic,eutopic and even normal endometrium,which mainly expressed in endometrial basal lacrimal duct,perivascular interstitial cells.There was also a small amount of NPY expression in myometrial vascular interstitial cells,but was not detected in blood vessels and ductal endothelial cells.Receptors Y1 and Y2 were also expressed in normal,ectopic and eutopic endometrium,expression including the basal layer of the endometrium,perivascular interstitial cells,and in the ductal endothelial cells.Y1 and Y2 mainly located on the cell membrane,and also a small amount of it in the cytoplasm.2)The results of immunohistochemistry also showed that NPY and its receptors Y1 and Y2 were high expression in the eutopic and ectopic endometrium of the research group were significant compared with the normal endometrium of the control group(P<0.001);NPY and its receptors Y1 and Y2 were increased in the research group with increasing pain degree,and there were statistically significant in the different subgroups of research group(P<0.05).3)Western Blot and Real-time PCR results showed that the expression of NPY and its receptors Y1 and Y2 in the ectopic and eutopic endometrium was statistically significant compared with the normal endometrium of the control group(P<0.05),and all subgroups were compared significantly due to the different pain scores in the different subgroups of research group(P<0.05).Conclusions:1)Endogenous NPY and its receptors Y1 and Y2 might be involved in the occurrence and development of endometriosis.2)The expression levels of endogenous NPY and its receptors Y1 and Y2 in eutopic endometrium > ectopic endometrium > normal endometrium,which supported the theory of "in situ decidual determinism";3)Endogenous NPY and its receptors Y1 and Y2 were closely related to the pain mechanism of endometriosis.Endogenous NPY may participate in the regulation of its pain mechanism through the agonist receptor Y2 and the inhibitoryreceptor Y1.Part II Investigate the Degree of Pain,Anxiety and Depression,Sexual Life Satisfaction and Quality of Life in Patients with Endometriosis Purpose:According to the investigation in degree of pain,anxiety and depression,sexual life satisfaction and quality of life in patients with endometriosis,we explore the relationship among endometriosis pain,anxiety and depression,and the impact of endometriosis pain,anxiety and depression on sexual life and quality of life.Methods:After the pathological diagnosed of open or laparoscopy surgery,108 patients with endometriosis as the research group were classified into three types according to the traditional classification: 31 with type peritoneal,53 with type ovarian,and 24 with type of deeply infiltrating endometriosis(DIE).A total of 102 normal examiners served as the control group.210 people were uniformly surveyed by standardized training personnel to complete the general situation questionnaire,A short form of the McGill pain questionnaire(SF-MPQ),Self-rating anxiety scale(SAS),Self-rating depression scale(SDS),Female sexual function index(FSFI)and The short form endometriosis health profile(EHP-5)questionnaires to test the degree of pain,anxiety and depression,satisfaction of sexual life and quality of life scores.Result:1)SF-MPQ measured pain degree including pain rating index sensory and emotional items,visual analog scale(VAS),current pain level,pain nature,pain frequency,pain duration in the research group was higher than the control one(P<0.05);Through the different pain characteristics of the three subtypes of the research group were compared,the pelvic pain and dysmenorrhea in the three subtypes were not significant statistically,but sexual pain score in type DIE was significantly higher than the other two subtypes(P<0.05).2)Both SAS and SDS scores of the research group were significantly higher than those of the control one(P<0.05).The DIE type score was slightly higher than the other two subtypes,but the SAS and SDS scores in the three subtypes were not statistically significant(P>0.05).3)The total score of FSFI in the research group was significantly lower than in the control.All the scores of six small items,such as sexual desire and sexual arousal,or lubricity,orgasm,satisfaction and pain,were significantly lower than those in the control(P<0.05).4)The EHP-5 score of the research group was significantly higher than in control one.In the research group,mood swing and the sexual pain were the most obvious in the module questionnaire.There were no significant differences in EHP-5scores between the mild and moderate pain group,the moderate and severe pain group,but the others had significant differences(P<0.05).Conclusions:1)There was no significant correlation between endometriosis pain and its lesion location.2)The degree of endometriosis pain was positively correlated with of anxiety and depression.3)The degree of endometriosis pain was negatively correlated with sexual life satisfaction;4)Some objective factors such as the marital status,menstrual history,birth history,education level,and economic income affected the quality of life of patients with endometriosis pain.And we found there was negative correlation between degree of pain,anxiety,depression and quality of life of patients with endometriosis pain.Part III Correlation between Serum NPY Expression and Pain,Anxiety and Depression in Patients with Endometriosis Purpose:To detect serum NPY expression in patients with endometriosis pain and in control group respectively.And to explore the relationship between serum NPY expression and degree of pain,anxiety and depression in patients with endometriosis.Method:Serum samples of 108 patients with endometriosis and 102 healthy controlswere collected all of whom participated in the questionnaire survey in part II.Serum NPY expression was detected by enzyme-linked immunosorbent assay(Elisa method).Result:1)The expression of serum NPY in patients with endometriosis was significantly higher than that in the control one(P<0.05).2)Serum NPY expression is up-regulated with the increasing of pain degree,and there were significant differences among the the different subgroups(P<0.05).3)The higher degree of anxiety and depression in patients with endometriosis pain,the higher the serum NPY expression level(P<0.05).Conclusions:Expression level of serum NPY was closely related to the degree of pain in endometriosis and the degree of anxiety and depression in patients with endometriosis pain.It had once again verified the correlation of endometriosis pain,anxiety and depression,which indicated that serum NPY expression was closely related to the body's stress state.In conclusion,we have explored that endogenous NPY and its receptors Y1,Y2 May be involved in the occurrence,development of endometriosis and are closely related to pain mechanisms of endometriosis,moreover,NPY is closely positive correlation with anxiety and depression caused by endometriosis pain.We think that NPY and its receptors Y1,Y2 may become new targets for the treatment of pain,anxiety and depression associated with endometriosis.