sprouted innervation into uterine transplants contributes to the development of hyperalgesia in a rat model of endometriosis发芽神经支配到子宫移植导致痛觉过敏的发展的子宫内膜异位大鼠模型.pdfVIP

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis . . Stacy L. McAllister , Natalia Dmitrieva , Karen J. Berkley* Program in Neuroscience, Florida State University, Tallahassee, Florida, United States of America Abstract Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropath