Anatomical changes in descending serotonergic projections from the rostral ventromedial medulla to the spinal dorsal horn following repetitive neonatal painful procedures

Anne R. de Kort*, Elbert A. Joosten, Eline M. Versantvoort, Jacob Patijn, Dick Tibboel*, Nynke J. van den Hoogen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Excessive noxious stimulation during the critical neonatal period impacts the nociceptive network lasting into adulthood. As descending serotonergic projections from the rostral ventromedial medulla (RVM) to the spinal dorsal horn develop postnatally, this study aims to investigate the long-term effect of repetitive neonatal procedural pain on the descending serotonergic RVM–spinal dorsal horn network. A well-established rat model of repetitive noxious procedures is used in which neonatal rats received four noxious needle pricks or tactile stimulation with a cotton swab per day in the left hind paw from day of birth to postnatal Day 7. Control animals were left undisturbed. When animals reached adulthood, tissue was collected for quantitative immunohistochemical analysis of serotonin (5-hydroxytryptamine, 5-HT) in the RVM and spinal dorsal horn. Both repetitive noxious and tactile procedures in the neonate decreased the 5-HT staining intensity in the adult ipsilateral but not contralateral spinal dorsal horn. Repetitive neonatal noxious procedures resulted in an increased area covered with 5-HT staining in the adult RVM ipsilateral to the side of injury, whereas repetitive neonatal tactile stimulation resulted in increased 5-HT staining intensity in both the ipsi- and contralateral RVM. The number of 5-HT cells in adult RVM is unaffected by neonatal conditions. This detailed anatomical study shows that not only neonatal noxious procedures but also repetitive tactile procedures result in long-lasting anatomical changes of the descending serotonergic system within the RVM and spinal dorsal horn. Future studies should investigate whether these anatomical changes translate to functional differences in descending serotonergic modulation after neonatal adverse experiences.

Original languageEnglish
Pages (from-to)361-371
Number of pages11
JournalInternational Journal of Developmental Neuroscience
Volume82
Issue number4
Early online date7 Apr 2022
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

Funding Information:
This work was financially supported by the Pain Knowledge Center from Maastricht and an institutional grant from University Maastricht, School Mental Health and Neuroscience. The primary rabbit anti‐5‐HT polyclonal antibody was kindly provided by Prof. H. W. M. Steinbusch, Department of Translational Neuroscience, Maastricht University, the Netherlands.

Funding Information:
This work was financially supported by the Pain Knowledge Center from Maastricht and an institutional grant from University Maastricht, School Mental Health and Neuroscience. The primary rabbit anti-5-HT polyclonal antibody was kindly provided by Prof. H. W. M. Steinbusch, Department of Translational Neuroscience, Maastricht University, the Netherlands.

Publisher Copyright:
© 2022 The Authors. International Journal of Developmental Neuroscience published by John Wiley & Sons Ltd on behalf of International Society for Developmental Neuroscience.

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