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Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review

  • Adenomyosis: Review
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Abstract

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers’ presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

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Data Availability

The data that support the findings of this study are available from the corresponding author, MSA, upon request.

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Acknowledgements

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Departamento de Ginecologia. Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

    Mariana da Cunha Vieira, Marina Paula Andres, Luiza Gama Coelho Riccio, Sara Schmitt Schlindwein & Mauricio Simões Abrão

  2. Gynecologic Division, BP - A Beneficencia Portuguesa de Sao Paulo, Rua Colombia 332, Sao Paulo, SP, Brazil

    Mariana da Cunha Vieira, Marina Paula Andres & Mauricio Simões Abrão

  3. Gynecologic Division, Hospital Do Servidor Do Estado, São Luís, MA, Brazil

    Fernanda Vieira Lins Arcoverde

  4. Gynecology and Obstetrics Unit, Department of Public Health, University of Naples Federico II, Naples, Italy

    Attilio Di Spiezio Sardo

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Correspondence to Mauricio Simões Abrão.

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da Cunha Vieira, M., Andres, M.P., Riccio, L.G.C. et al. Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01587-8

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