The Potential Role of Endometrial Nerve Fibers in the Pathogenesis of Pain During Endometrial Biopsy at Office Hysteroscopy

Abstract

We aimed to evaluate whether nerve fibers are present in the endometrial layer of patients submitted to office hysteroscopy and their potential contribution to the pathogenesis of pain during that procedure. Through a prospective case-control study performed in tertiary centers for women's health, endometrium samples were collected during operative office hysteroscopy from 198 cycling women who previously underwent laparoscopy and/or magnetic resonance imaging investigation for infertility assessment. Samples were classified according to the degree of the pain patients experienced and scored from values ranging from 0 (absence of discomfort/pain) to 10 (intolerable pain) on a 10-cm visual analog scale (VAS). The presence of nerve fiber markers (S100, NSE, SP, VIP, NPY, NKA, NKB, NKR1, NKR2, and NKR3) in the endometrium was also evaluated by morphologic and immunohistochemical analyses. We found that S-100, NSE, NKR1, NK-A, NK-B, VIP, and NPY, were immunolocalized in samples of endometrium, in significantly (P < .01, for all) higher levels in samples collected from patients with VAS score > 5 (group A) than ≤ 5 (group B) and significantly (P < .0001 for all) positively correlated with VAS levels. A statistically significant (P = .018) higher prevalence of endometriosis and/or adenomyosis was depicted in patients of group A than group B. Data from the present study led us to conclude that nerve fibers are expressed at the level of the functional layer of the endometrium and may contribute to pain generation during office hysteroscopy, mainly in women affected by endometriosis and adenomyosis.

Neuroangiogenesis in endometrium of women with endometriosis and chronic pelvic pain: high expression of vasoactive intestinal peptide

“…Di Spiezio Sardo и соавт. [21]. Авторы исследовали экспрессию панели маркеров нервных волокон в эндометрии у женщин с и без эндометриоза/аденомиоза, у которых боль была более 5 баллов по шкале ВАШ.…”

“…Метаанализ биомаркеров эндометрия для оценки роли боли у больных с эндометриозом установил VIP как «перспективный маркер для дальнейшего исследования» [21].…”

Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents

“…Studies have shown that women with endometriosis and pain have growths with greater nerve fiber density than woman with endometriosis without pain (Di Spiezio Sardo et al, 2015; Yao et al, 2010). In another study, a positive correlation was found between pain severity and cyst nerve fiber density (Mechsner et al, 2009).…”

“…One possibility is that the growth's sprouted sensory and sympathetic nerve supply opens a two-way line of communication between the growths and CNS that is capable of generating pain (Stratton and Berkley, 2011). Studies in the rodents (Alvarez et al, 2012; McAllister et al, 2009, 2012) and a few clinical studies support this hypothesis (Di Spiezio Sardo et al, 2015; Mechsner et al, 2009; Wang et al, 2010). …”

Analgesia para raspagem endometrial em mulheres com subfertilidade: ensaio clínico controlado com alocação aleatória das participantes

“…Fibras nervosas têm expressão na camada funcional do endométrio e podem contribuir para o estímulo doloroso durante a manipulação da cavidade (46). Estudos atuais, revisionais, já publicados ou em andamento, associam injúria endometrial à dor como efeito adverso (37,(47)(48)(49), e suas consequências, inclusive o reflexo vasovagal (40).…”