Increased Nerve Density in Deep Infiltrating Endometriotic Nodules

Abstract

Background/Aims: Deep infiltrating endometriosis is a very painful condition and the mechanism of pain is still poorly understood. Pain and hyperalgesia can partly be explained by an increased number of nerve structures in the painful lesion. In order to clarify this issue, we assessed the nerve density in deep infiltrating endometriotic nodules of the posterior vagina and in the adjacent healthy vaginal tissue of the same patient. Methods: A prospective clinical and pathological study of 31 cases of deep infiltrating vaginal endometriotic nodules was conducted. Fifteen patients were in the proliferative phase and 16 in the secretory phase. The nerve density was studied by immunohistochemistry with the monoclonal antibody NF against neurofilaments in deep infiltrating endometriosis and in the adjacent unaffected vaginal tissue in the proliferative and in the secretory phases. Neurofilaments constitute the main structural elements of neuronal axons and dendrites. Results: The nerve density was significantly different in the endometriotic nodule than in the adjacent unaffected vaginal tissue (p = 0.0013). The same significant difference was found between endometriotic nodules and the unaffected vagina in the proliferative phase (p = 0.009) and in the secretory phase (p = 0.04). This difference was not significant between the proliferative and the secretory phases in the endometriotic lesions and in the controls. Conclusions: We hypothesize that the significantly increased number of nerve structures in the endometriotic nodules may contribute to the occurrence of severe and neuropathic pain that characterizes these lesions

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis

“…As previously reported, MCs also play a pivotal role in the control of angiogenesis and neurogenesis, key features of ENDO. 4,32,55 For this reason, we first studied the role of ultramicronized PEA in angiogenesis during ENDO. Here, for the first time, we demonstrate a strong antiangiogenic role of ultramicronized PEA in this condition, since histological analysis of ENDO cysts from animals receiving the compound revealed a significant reduction of blood vessels compared with placebo-treated animals.…”

Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

“…Endometriotic lesions are heavily innervated (21, 22), and studies in women and rats suggest that innervation is involved in endometriosis-associated pain (5, 21, 23, 24). Dual staining with GFP and a pan-neuron marker, protein gene product 9.5 (PGP 9.5), indicated that EGFP host-derived neurons were present in wild-type lesions.…”

“…Although the hormonal mechanisms involved are not fully understood, observations in the clinic and in a rat model suggest that nerve fiber density innervating endometriotic tissue is correlated with pain (5, 21). In our model, newly established blood vessels, nerve fibers, and infiltrating immune cells were colocalized in ectopic tissue.…”

Anatomical Distribution of Deep Infiltrating Endometriosis and Its Relationship to Pelvic Pain

“…The association between rectovaginal DIE and deep dyspareunia may be explained by the invasive behavior of the disease. 22,23 The available published literature to date reports different findings with regard to anatomical location and pelvic pain. The most frequent symptoms of pelvic endometriosis are dysmenorrhea, dyspareunia, CPP, and infertility.…”