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      Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain

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          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.


          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.


          This study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named “neuroangiogenesis”.

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          Most cited references 42

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          Neuronal plasticity: increasing the gain in pain.

          We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
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            The pains of endometriosis.

            Endometriosis is a disease defined by the presence of endometrial tissue outside of the uterus. Severe pelvic pain is often associated with endometriosis, and this pain can be diminished with therapies that suppress estrogen production. Many women with endometriosis also suffer from other chronic pain conditions. Recent studies suggest that mechanisms underlying these pains and sensitivity to estrogen involve the growth into the ectopic endometrial tissue of a nerve supply, which could have a varied and widespread influence on the activity of neurons throughout the central nervous system.
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              Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain.

              In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                25 September 2018
                : 11
                : 1999-2009
                [1 ]Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China, yszlfy@ 123456163.com
                [2 ]Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
                Author notes
                Correspondence: Shuzhong Yao, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, The 2nd Zhongshan Road, Yuexiu District, Guangzhou 510080, Guangdong Province, China, Tel +86 1 360 283 4127, Email yszlfy@ 123456163.com
                © 2018 Liang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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