Different Innervation Of Endometriosis Lesions And The Relationship With Pelvic Pain

BackgroundEndometriosis is the activity with the growth of endometrium outside the uterine cavity.Endometriosis lesions are widely distributed,with the formation of nodules, cysts and other pathological forms,giving rise to different clinical symptoms,such as dysmenorrhea,infertility,pelvic mass,and so on.Of which pain is the most important clinical symptoms,about 70～80%of patients suffering from different forms of varying degrees of pain,such as dysmenorrhea,anus falling pain,bowel pain,painful sexual intercourse,such as chronic pelvic pain.Endometriosis pain is heavy,takes many forms, lasts for a long time,severely affects the quality of life of patients.At present,the mechanism of pain in endometriosis is not yet clear.Oppression,pain factor secretion as well as the role of inflammatory factors may be involved in the process of its occurrence. Our clinical study showed that the degree of pain has no correlation with disease stage, but the distribution of lesions esp.post-pelvic lesions of endometriosis are more obvious cause dysmenorrhea,anal falling deep intercourse pain and pain symptoms,including ectopic endometrial glands and stromal invasion depth of the uterosacral ligament, uterine and rectal fossa rectal vaginal septum and other parts.Changes in neural anatomy is an important mechanism leading to pain,noxious stimulation factor,nerve fibers,neurotransmitters and abnormal signal transduction pathway may function individually or jointly in the course of the occurrence of pain. Foreign scholars has applies neuroanatomy to endometriosis pain,such as the author in 2005 SCIENCE magazine that endometriosis pain is caused by the dominate the formation of nerve fibers.Several other studies have also found that in peritoneal endometriosis lesions and nodules in the recto-vaginal septum the number of nerve fibers increase and the invasion of the perineurium by interstitial cells.But these research sample are not large and lack of a comprehensive multi-level research in the relationship of nerve and pain.Our research topics are about the nerve fibers distribution in different types of endometriosis lesions and the clinical relevance of pain.We also observe the spatial distribution of nerve fibers with ectopic glands, stromal,neovascularization and pain.This research about the neural mechanisms of endometriosis pain can provide new ideas to clinical treatment and basis research.Objective1,Comparison of the innervation in different types of endometriosis lesions(including peritoneal endometriosis,ovarian endometriosis,uterosacral ligament endometriosis crux section,uterine endometriosis rectal crux of Waterloo Festival,vaginal septum endometriosis rectal crux section),to explore its relationship with endometriosis pain symptoms.2,Observation of morphology and ultrastructure of nerve fibers in endometriosis tissue.To analyse the the spatial relationship of nerve fibers and ectopic endometrial glands or stroma,angiogenesis,inflammatory factors,estrogen receptors, neuron-specific enolase.To further investigate the abnormal distribution of nerve fibers arising from endometriosis of the possible mechanisms of pain.3,Comparison of the distribution of nerve fiber and the expression of neuron-specific enolase in endometrial tissue of endometriosis and non-endometriosis patients.To explore the differences of the uterine endometrium may play a role in endometriosis neuroanatomy of pain mechanisms.4,Comparison the expression of nerve protein,neurotransmitter,neuron-specific enolase in serum and ascites of endometriosis and non-endometriosis patients.To explore a new simple and practical means of clinical detection.Methods1,Immunohistochemical detection the distribution of different nerve fibers in different endometriosis organizations,including the peritoneal lesions of endometriosis, ovarian endometriosis cyst wall,uterosacral ligament endometriosis,uterine fossa rectal endometriosis and vaginal septum endometriosis,as well as the normal peritoneal,ovarian mature cystic teratoma wall,normal uterosacral ligament.2,Analysis software to count nerve fibers and the relevance of differences in the number with symptoms and pain,of clinical staging.3,Real-time PCR used to detect the expression of neural tissue marker protein(S-100) in endometriosis.4,Transmission electron microscopy observation of nerve fibers in endometriosis lesions.Observation of the spatial distribution of nerve fibers and ectopic endometrial glands or stroma and analysis the pain related to each other.5,Immunohistochemistry of spatial distribution of neovascularization compared with the nerve fibers in serial endometriosis tissue sections.6,Immunohistochemical double labeling fluorescence observation of nerve fibers and inflammatory factors,estrogen receptor,as well as neuron-specific enolase expression in endometriosis tissue.7,Real-time PCR used to detect expression neuron-specific enolase in endometriosis tissue.8,Immunohistochemical method,method of fluorescent labeling of immune cells, Real-time PCR comparing the expression of nerve fiber,neuron-specific enolase in endometriosis and non-endometriosis patients9,ELISA methods for the detection the expression levels of S-100 protein,SP and neuron-specific enolase in serum and ascites of endometriosis and non-endometriosis patients.Results1,Peritoneal endometriosis lesions is higher than the number of nerve fibers in normal peritoneum.The number of nerve fibers in uterosacral ligament endometriosis is significantly higher than the normal uterosacral ligament organizations,Expression of nerve fibers in ovarian endometriotic cyst wall is free expression or only a small amount.2,The number of nerve fibers different endometriosis tissues is significantly different,from high to low as follows:uterosacral ligament(29.74±17.33)＞vaginal septum endometriosis(24.53±13.34)＞uterus rectum crux(17.09±10.09)＞peritoneal endometriosis lesions(6.77±4.21)＞endometriosis ovarian cyst wall (0.07±0.25).3,The number of nerve fibers of endometriosis is correlated to the degree of pain,and in the clinical stage and no significant correlation;Number of nerve fibers in peritoneal endometriosis lesions with a certain degree of dysmenorrhea associated with falling anal pain,painful sexual intercourse,the degree of chronic pelvic pain was no significant correlation;Number of nerve fibers in endometriosis ovarian cyst wall with dysmenorrhea,anus falling pain,pain in the degree of sexual intercourse was no significant correlation;Number of nerve fibers of uterosaeral ligament with dysmenorrhea,painful intercourse significantly associated with falling anal pain,chronic pelvic pain have some relevance;Number of nerve fibers in rectal uterine crux endometriosis and the falling anal pain, painful sexual intercourse with a significant correlation,with dysmenorrhea and chronic pelvic pain in a certain degree of correlation;Number of nerve fibers in rectal vaginal septum endometriosis and the falling anal pain,painful sexual intercourse with a significant correlation,dysmenorrhea with some relevance,and chronic pelvic pain no significant correlation.After the application of GnRHa drugs,number of nerve fibers in endometriosis tissues significantly decrease;4,New and irregular peripheral nerve fibers increase in endometriosis tissues,and ultrastructure changed:increased concentration of Schwann cell staining,myelin staining shallow,suggesting that newborn neurons,without myelin increase.5,Nerve fibers and the ectopic endometrial glands or stroma ranging from 0-2000um and the length and degree of pain was a negative correlation;Nerve fibers and vascular spatial distribution is consistent,and with the estrogen receptor and COX-2 expression in a certain degree of correlation;Neuron-specific enolase expression in nerve fibers and ectopic endometrial glandular epithelial cells.6,Patients with endometriosis eutopic endometrial nerve fibers and neuron-specific enolase expression while ectopic lesions was significantly lower than that,but were significantly higher than non-endometriosis patients.7,The lever of S-100,SP,NSE in serum is low in Endometriosis non-endometriosis patients fluid,and has no significant differenc.but the lever in acites of endometriosis are higher.Conclusion1,This study proved the distribution of nerve fibers in different endometriosis tissues and the relationship with pain,from the neural mechanisms explained the neuro anatomy of endometriosis and pelvic pain2,The study found that the distancenerve fibers to ectopic endometrial glands or stroma has negative correlation with pain,suggesting that endometriosis lesions on the nerve stimulation may be an important reason for the occurrence of pain.3,Hyperplasia of newborn non-myelin nerve fibers and angiogenesis in endometriosis lesions suggesting that the process in the event of the two may interact,and participate in the occurrence and development of lesions.4,The study found that neuron-specific enolase expression level in newborn glandular epithelial cells is significantly higher than normal tissue,suggesting that endometriosis lesions of endometrial glandular epithelial cells may have the neuro-endocrine characteristics,and may be related to invasion of ectopic endometrial growth and nerve distribution.5,Nerve fibers and neuron-specific enolase expression in eutopic endometrial significantly higher than the normal endometrium,and further confirmed that the "eutopic endometrial determinism".6,Nerve protein and neuron-specific enolase in endometriosis and non-endometriosis patients with no difference in detection,suggesting that the expression of proteins in the nerve localized in lesions,may not be the ideal means of clinical detection.