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
PloS one · 2012 · vol. 7(2) , pp. e31758 · doi:10.1371/journal.pone.0031758 · PMID:22363725 · PMC3283674 · W2056634842
article OA: gold CC0 ⤵ 48 in-corpus citations
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In a rat endometriosis model, ectopic uterine transplants acquired sensory and sympathetic innervation, which became abnormally active and preceded the development of vaginal hyperalgesia.

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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/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Hyperalgesia Hyperalgesia Uterus Uterus Animals Behavior, Animal Cysts Cysts Cysts Cysts Disease Models, Animal Endometriosis Evans Blue Female Hyperalgesia Immunohistochemistry Rats Rats, Sprague-Dawley

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