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

M Vieira, Marina Paula Andres, Luiza Gama Coelho Riccio, Sara Schmitt Schlindwein, Fernanda Vieira Lins Arcoverde, Attilio Di Spiezio Sardo, Maurício Simões Abrão
Reproductive sciences (Thousand Oaks, Calif.) · 2024 · vol. 31(8) , pp. 2137–2149 · doi:10.1007/s43032-024-01587-8 · PMID:38720155 · W4396747456
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-07 ⓘ

This systematic review found decreased or absent antiprotein gene product 9.5 in adenomyosis endometrium, inconsistent neurofilament staining, and heterogeneous nerve growth factor results, with preliminary data suggesting increased uterine nerve fibers.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This paper is a systematic review (searching Embase, PubMed/Medline, and Cochrane through November 2023) evaluating whether uterine nerve fibers’ presence and density in women with adenomyosis are associated with pain. Ten studies comparing uterine biopsy tissue from women with versus without adenomyosis were included; most reported decreased or absent antiprotein gene product 9.5 in adenomyosis, but no included study found differences in neurofilament staining between groups. Studies assessing nerve growth factor staining varied, with one showing no differences across endometrial layers, another reporting increased staining in the adenomyosis functional layer, and a third reporting overexpression of NGF, synaptophysin, and MAP2 mRNA in focal adenomyosis, while preliminary data from low-quality studies suggested increased nerve fiber density. This paper centrally about endometriosis; it does not explicitly discuss endometriosis or adenomyosis?

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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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Condition tags

dysmenorrheachronic_pelvic_painadenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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