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Repetitive daily oxytocin treatment reduces weight gain but not acute neonatal procedural pain

Pediatric Research volume 98, pages 294–300 (2025)Cite this article

Abstract

Background

While the incidence of neonatal intensive care unit (NICU) admission steadily increases, neonatology lacks evidence of a safe, effective, and preventive analgesic for treating procedural pain. Given its role in nociception and promoting healthy neurodevelopment, the endogenous neuropeptide oxytocin (OT) emerges as a promising candidate.

Methods

This study investigates the use of daily repeated subcutaneous OT (1 mg/kg) treatment in an established model of neonatal repetitive procedural pain and assesses the effectivity of OT treatment on mechanical sensitivity and body weight.

Results

Contrary to our hypothesis repeated daily OT treatment did not prevent the development of mechanical hypersensitivity following needle pricks. Furthermore, treatment with OT diminished body weight gain in neonatal pups, a major side effect observed throughout the neonatal week. These results highlight the unique nature of the maturing nociceptive system that makes the identification and selection of analgesic options for the treatment of acute neonatal procedural pain a major challenge.

Conclusion

In conclusion, our preclinical results do not support the use of repeated OT for acute pain relief in the NICU, and the side effects on body weight gain raise concerns about the use of OT in the NICU.

Impact

  • Repeated daily OT treatment inhibits weight gain in neonatal rat pus.

  • Repetitive daily OT administration does not prevent the development of mechanical hypersensitivity in a model of neonatal procedural pain.

  • Future research must focus on the unique physiology of the developing nociceptive system to establish safe, effective and protective treatment of neonatal procedural pain.

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Fig. 1: Experimental design and timeline.
Fig. 2: Mechanical sensitivity during the neonatal week.
Fig. 3: Effect of daily repeated OT injection on body weight.
Fig. 4: Pups development throughout the neonatal week.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The completion of this research project would not have been possible without the scientific discussions with colleagues L. Heijmans (Ph.D.), T.J. de Geus (MSc), I. Rudnick-Jansen (Ph.D.), G. Franken (Ph.D.). Contribution from D. Mulder-Jongen and D. Hermes, and members of the animal facility was also essential in the completion of this research. The authors have no conflict of interest to declare. Funding was provided by internal research support based on grants from Erasmus-Sophia Children’s Hospital Rotterdam, the Netherlands (to S. H.P. Simons) and Maastricht University, Maastricht, the Netherlands (to E.A.J. Joosten). All animal experiments were performed in accordance with the European Directive for Protection of Vertebrate Animal Use for Experimental and Other Scientific Purposes (86/609/EEC) and were approved by the Committee for Experiments on Animals, Maastricht, The Netherlands (DEC 2017-017).

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Management, Maastricht University Medical Centre+, Maastricht, the Netherlands

    Mathilde Baudat & Elbert A. J. Joosten

  2. Department of Translational Neuroscience, Institute of Mental Health and Neuroscience Research, Maastricht University, Maastricht, the Netherlands

    Mathilde Baudat & Elbert A. J. Joosten

  3. Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Centre Rotterdam- Sophia Children Hospital, Rotterdam, the Netherlands

    Sinno H. P. Simons

Authors
  1. Mathilde Baudat
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  2. Elbert A. J. Joosten
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  3. Sinno H. P. Simons
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Contributions

All authors substantially contributed to the conception and design of the experiment, interpreted the data and critically revised the manuscript. Acquisition of data and drafting of the article was performed by M. Baudat. The final manuscript was approved by all authors.

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Correspondence to Mathilde Baudat.

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Baudat, M., Joosten, E.A.J. & Simons, S.H.P. Repetitive daily oxytocin treatment reduces weight gain but not acute neonatal procedural pain. Pediatr Res 98, 294–300 (2025). https://doi.org/10.1038/s41390-024-03680-9

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