Inflammation and nerve fiber interaction in endometriotic pain.

Endometriosis is an extremely prevalent estrogen-dependent condition characterized by the growth of ectopic endometrial tissue outside the uterine cavity, and is often presented with severe pain. Although the relationship between lesion and pain remains unclear, nerve fibers found in close proximity to endometriotic lesions may be related to pain. Also, women with endometriosis pain develop central sensitization. Endometriosis creates an inflammatory environment and recent research is beginning to elucidate the role of inflammation in stimulating peripheral nerve sensitization. In this review, we discuss endometriosis-associated inflammation, peripheral nerve fibers, and assess their potential mechanism of interaction. We propose that an interaction between lesions and nerve fibers, mediated by inflammation, may be important in endometriosis-associated pain.

The potential role of endometrial nerve fibers in the pathogenesis of pain during endometrial biopsy at office hysteroscopy

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.