25: Investigating Placental Transcriptomic Adaptations to Maternal Neuropathic Pain During Pregnancy

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Neuroimmunology, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics), Genetics and Epigenetics, Behavioral studies

Background and Aims: Chronic pain is highly prevalent during pregnancy yet remains under-treated due to limited pharmacological options and concerns about fetal exposure. As a result, many individuals experience persistent pain throughout gestation, but its biological impact on the maternal-fetal interaction is poorly understood. The placenta regulates fetal exposure to maternal signals, including nutrients, hormones, and immune mediators, and its function is shaped by maternal physiological state. Unlike other maternal stressors, pain may represent a distinct condition with unique effects on placental function and integrity. We therefore aimed to determine how gestational neuropathic pain affects fetal development and placental gene expression, with the goal of identifying molecular adaptations at the maternal-fetal interface.

Methods: Female CD-1 mice underwent unilateral spared nerve injury (SNI) prior to conception to model chronic neuropathic pain during pregnancy. At gestational day 10.5 and 16.5 (GD10.5 and GD16.5), mechanical hypersensitivity and locomotor activity were assessed using the von Frey Test and Open Field Test, respectively. Anxiety-like behaviour was assessed at GD15.5 using the Elevated Plus Maze test. At G16.5, placental tissue and fetuses were collected. Fetal sex was determined by genotyping to allow analysis of sex-specific placental changes. Placental samples were for bulk RNA sequencing, followed by differential gene expression analysis to identify pain-associated transcriptional changes.

Results: Mice that received SNI developed sustained mechanical hypersensitivity relative to controls, confirming induction of a chronic pain state. Mice that received the sham surgery had reduced mechanical hypersensitivity at G10.5 and G16.5, but not immediately before conception. Pregnant sham mice also displayed increased time spent in the open arms of the Elevated Plus Maze, while this effect was not observed in the pregnant SNI group. Maternal neuropathic pain did not alter pregnancy trajectory measures such as time to conception, gestational weight gain, litter size or fetal weight. Although no group differences were detected in physiological pregnancy outcomes, placental tissue was collected for bulk RNA-seq analysis to determine whether maternal neuropathic pain induces molecular adaptations at the placental level.

Conclusions: Although chronic pain is highly prevalent during pregnancy, its management remains challenging due to limited pharmacological options and concerns regarding fetal exposure. This study addresses a gap in understanding how unmedicated chronic pain during gestation influences placental biology and the fetal environment. Our findings suggest that SNI reliably induces a persistent maternal pain state, while leaving gross pregnancy trajectory measures unaffected. This suggests that maternal neuropathic pain may not explicitly disrupt pregnancy progression but could still influence fetal development through more subtle placental mechanisms. By examining placental transcriptomic profiles, this work may reveal molecular adaptations that are not captured by conventional pregnancy outcomes, offering insight into how maternal pain states shape the fetal environment.

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Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020;11:575197. doi:10.3389/fimmu.2020.575197
Liu C, Liu H, Li H, et al. Prenatal stress increases corticosterone levels in offspring by impairing placental glucocorticoid barrier function. Torrens C, ed. PLoS One. 2025;20(7):e0313705. doi:10.1371/journal.pone.0313705
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Presenting Author: Julia Schneider Krimberg
Submitting Author: Julia Schneider Krimberg

Senior Author: Loren Martin

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Maryam Fazili: HBSc - University of Toronto
• Evana Xiau: MSc - Univeristy of Toronto
• Lara Ramadan: NA - Univeristy of Toronto
• Damien Boorman: PhD - Univeristy of Toronto
• Loren Martin: PhD - Univesity of Toronto