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Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain

Authors Liang Y, Liu D, Yang F, Pan W, Zeng F, Wu J, Xie H, Li J, Yao S

Received 20 March 2018

Accepted for publication 25 June 2018

Published 25 September 2018 Volume 2018:11 Pages 1999—2009

DOI https://doi.org/10.2147/JPR.S168715

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 6

Editor who approved publication: Dr E Alfonso Romero-Sandoval


Yanchun Liang,1 Duo Liu,1 Fan Yang,1 Wenwei Pan,1 Feitianzhi Zeng,1 Jinjie Wu,2 Hongyu Xie,2 Jiaying Li,2 Shuzhong Yao1

1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

Purpose: Recent studies have shown that abnormal distribution of pelvic nerves contributes to endometriosis-associated pain. However, the relationship between neurogenesis and pain severity in endometriosis still remains uncertain, which makes it an enigma for both gynecologists as well as neuropathologists. In this study, we tried to explore a special phenomenon, perineural invasion (PNI), in deep infiltrating endometriosis (DIE) and investigated the correlation between PNI- and DIE-associated pain.
Patients and methods: The study was conducted in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Sun Yat-sen University from June 2012 to January 2015. In total, 64 patients with DIE were enrolled. They received laparoscopically surgical resection of endometriotic lesions. The Kruskal–Wallis and Mann–Whitney tests were used for comparisons of enumeration data. Spearman rank correlation was used for linear analysis.
Results: Immunohistochemical analysis demonstrated that PNI was commonly found in DIE lesions. Patients were divided into PNI (+) group and PNI (−) group. The visual analog scale scores of dysmenorrhea, dyspareunia, and chronic pelvic pain were higher in PNI (+) group than in PNI (−) group. Also, we found significantly increased density of newly formed nerve fibers as well as microvessels in lesions of PNI (+) group. Further, double immunofluorescence showed a closely spatial nerve–vessel network in the endometriotic lesion of PNI (+) group. More importantly, correlation analysis revealed positive relation between the density of newly formed nerve fibers in the lesion and the density of microvessels in lesions of PNI (+) group.
Conclusion: This study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named “neuroangiogenesis”.

Keywords: perineural invasion, deep infiltrating endometriosis, pain, neuroangiogenesis

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