Comparison of Nerve Fiber Density between Patients with Uterine Leiomyoma with and without Pain: a Prospective Clinical Study

Abstract

Introduction We aimed to compare the presence and the amount of nerve fibers in endometrial, myometrial and leiomyoma tissues using protein gene product 9.5 (PGP 9.5) and neurofilament (NF) immunohistochemical staining in uterine leiomyoma patients with and without pain complaint. Methods Patients undergoing hysterectomy for uterine leiomyoma were prospectively enrolled in the study. Twenty-five uterine leiomyoma patients without pelvic pain complaint (visual analog scale (VAS) < 5) were assigned to Group 1; 23 uterine leiomyoma patients with pelvic pain complaint (VAS ≥ 5) were assigned to Group 2. Endometrial, myometrial and leiomyoma tissues obtained from hysterectomy specimens were stained immunohistochemically using PGP 9.5 and NF dyes. The presence and density of nerve fibers were compared between the two groups. Results None of the endometrial samples in either groups stained with PGP 9.5 and NF dyes. There was no statistically significant difference in the number of nerve fibers in myometrial and leiomyoma tissues between the two groups with either of the stains (PGP 9.5: p = 0.39 and p = 0.29; NF: p = 0.83 and p = 0.65, respectively). There was agreement between PGP 9.5 and NF immunohistochemical staining for nerve fiber detection in myometrial and leiomyoma tissues (p < 0.05/κ = 0.622 and p < 0.05/κ = 0.388, respectively). Conclusion This study demonstrates that the quantity and density of nerve fibers in myometrial and leiomyoma tissue in patients with pain were similar to that in patients without pain.

Increased expression of neurogenic factors in uterine fibroids

“…To this regard, NGF has a pivotal role in the generation of pain and hyperalgesia in many acute and chronic pain states (Hefti et al, 2006;Donnez and Dolmans, 2016); therefore, it may be suggested that, also in fibroids, pelvic pain along with dysmenorrhea may depend on these factors. Even though a significant increase in density of small nerve fibers in the myometrium of women with endometriosis and chronic pelvic pain, along with perivascular nerve fiber proliferation, was detected (Tokushige et al, 2007); more recently published data demonstrated that the quantity and density of nerve fibers in myometrial and leiomyoma tissue in patients with pain were similar to those in patients without pain (Giray et al, 2018) The expression of NGF, MAP-2 and SYP was upregulated in adenomyosis (Carrarelli et al, 2017) and in deep infiltrating endometriosis (Gori et al, 2016), correlated with pain, a typical symptom of uterine disorders; the present study demonstrates a significant increase of all the selected neurogenic markers also in uterine fibroids.…”

A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

“…The ECM content varies in different ULs and is presumably subject to change as the myoma progresses and undergoes involution [ 14 ]. The main cellular components of a UL are smooth muscle cells, fibroblasts and vascular endothelial cells; other detected cellular components include blood cells, neurons and telocytes [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids

“…The McGill Pain Questionnaire collected detailed data about the pain associated with fibroids and evaluated the impact on pain from the study drug injection [35,36]. The visual analogue scale (VAS) for pain was used to evaluate fibroid-related pain on a 0-10 Likert scale (higher score = worse pain) [37,38]. The questionnaires were administered at baseline and post-study drug injection to assess fibroid-related symptoms such as menorrhagia and pain.…”