Background & Aims

Prenatal stress has been substantiated to exert adverse effects on the progression of pregnancy, as well as on fetal health and development, even after birth (1). Neuropathic pain (NP), a chronic pain resulting from damage to the somatosensory nervous system, is less well tolerated in females (2). Given its chronic nature and associated comorbidities such as anxiety and depression, NP may be considered a prenatal stress factor when occurring in pregnant women (3). However, its comprehensive effects on pregnancy and offspring remain not fully elucidated.
Our study aims to evaluate the impact of NP during pregnancy on tactile sensitivity and nociception of the offspring, while also exploring broader neurodevelopmental aspects such as depressive and anxiety-related traits as well as cortisol levels through a stress test. Intersex variability is also investigated.

Methods

Thirteen female rats were included in this study. Before mating, 8 female rats underwent spared nerve injury (SNI) surgery to establish a NP model, and 5 sham surgery (Sham). Tactile sensory testing of rat mothers was assessed pre and postoperatively, as well as during the 3 weeks of pregnancy, using cold acetone (CA), Von Frey (VF) and Pinprick (PP) tests.
After birth, the offspring of SNI (n=81) and of Sham (n=58) mothers were subjected to:
1. Pain assessment (CA, VF, PP and a thermal hyperalgesia test (HG-Hargreaves)
2. Assessment of anxiety (elevated plus maze and novelty suppressed feeding) and depression-like behaviors (sucrose preference and forced swim tests)
[Analysis 1 and 2 were done at juvenile and adolescent ages, and included 40 offspring, divided into 24 rats from SNI mothers (12 male); and 16 rats from Sham mothers (8 male)]
3. Cortisol variation during restraint stress test at the age of 2 months, including n=14 males, 7 from SNI mothers, and 7 from Sham.

Results

Data reveals pregnancy-induced allodynia in SNI mothers a week before birth, confirmed by VF and CA tests (p=0.04 and 0.05 respectively) compared to post-op scores, although hyperalgesia persists.
A notable disparity in sex ratio was observed, showing a higher prevalence of male offspring from mothers with SNI. Offspring of SNI mothers were more sensitive to heat stimuli and VF mechanical stimuli, both during juvenile and adolescent periods (p<0.00). They also displayed more pronounced anxiety behavior than Sham mothers’ offspring (p=0.08 juvenile EPM). Moreover, female offspring of SNI mothers were more sensitive than males of the same group (p=0.02 in juvenile for HG; p=0.01 in juvenile and p<0.00 in adolescent for VF), while adolescent males from SNI mothers were more anxious than females (p=0.01 EPM). An increase in cortisol levels during a stressful event seems to be more pronounced in the offspring of SNI mothers, without reaching statistical significance.

Conclusions

This study affirms the detrimental effects of prenatal NP on offspring and underscores the importance of exploring these observations in a human clinical context. It also highlights the necessity to develop effective therapeutic strategies for NP, especially in the delicate context of pregnancy, as conventional therapies may interfere with gestation.

References

1.Coussons-Read ME. Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstet Med. 2013 Jun;6(2):52–7.
2.Miclescu AA, Gkatziani P, Granlund P, Butler S, Gordh T. Sex-related differences in experimental pain sensitivity in subjects with painful or painless neuropathy after surgical repair of traumatic nerve injuries. Pain Rep. 2022;7(6):e1033.
3.Ray-Griffith SL, Wendel MP, Stowe ZN, Magann EF. Chronic pain during pregnancy: a review of the literature. Int J Womens Health. 2018;10:153–64.

Presenting Author

Sandra Kobaiter Maarrawi

Poster Authors

Nizar El Bcherawi

MSc

Saint Joseph University of Beirut – Lebanon, Faculty of Medicine, LAREN

Lead Author

Sandra Kobaiter

PhD

Saint Joseph University of Beirut - Lebanon

Lead Author

Farid Mallat

BSc

Saint Joseph University of Beirut – Lebanon, Faculty of Medicine, LAREN

Lead Author

John-Victor El Khoury

BSc

Saint Joseph University of Beirut – Lebanon, Faculty of Medicine, LAREN

Lead Author

Zeinab Meshsein

PhD

Saint Joseph University of Beirut – Lebanon, Faculty of Medicine, LAREN

Lead Author

Joseph Maarrawi

MD

Saint Joseph University of Beirut – Lebanon, Faculty of Medicine, LAREN

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral