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

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