Cargando…

Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain

Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive...

Descripción completa

Detalles Bibliográficos
Autores principales: de Kort, Anne R., Joosten, Elbert A., Patijn, Jacob, Tibboel, Dick, van den Hoogen, Nynke J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091564/
https://www.ncbi.nlm.nih.gov/pubmed/35571143
http://dx.doi.org/10.3389/fpain.2022.872587
_version_ 1784704950643720192
author de Kort, Anne R.
Joosten, Elbert A.
Patijn, Jacob
Tibboel, Dick
van den Hoogen, Nynke J.
author_facet de Kort, Anne R.
Joosten, Elbert A.
Patijn, Jacob
Tibboel, Dick
van den Hoogen, Nynke J.
author_sort de Kort, Anne R.
collection PubMed
description Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0–7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates.
format Online
Article
Text
id pubmed-9091564
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90915642022-05-12 Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain de Kort, Anne R. Joosten, Elbert A. Patijn, Jacob Tibboel, Dick van den Hoogen, Nynke J. Front Pain Res (Lausanne) Pain Research Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0–7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9091564/ /pubmed/35571143 http://dx.doi.org/10.3389/fpain.2022.872587 Text en Copyright © 2022 de Kort, Joosten, Patijn, Tibboel and van den Hoogen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pain Research
de Kort, Anne R.
Joosten, Elbert A.
Patijn, Jacob
Tibboel, Dick
van den Hoogen, Nynke J.
Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title_full Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title_fullStr Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title_full_unstemmed Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title_short Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain
title_sort selective targeting of serotonin 5-ht1a and 5-ht3 receptors attenuates acute and long-term hypersensitivity associated with neonatal procedural pain
topic Pain Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091564/
https://www.ncbi.nlm.nih.gov/pubmed/35571143
http://dx.doi.org/10.3389/fpain.2022.872587
work_keys_str_mv AT dekortanner selectivetargetingofserotonin5ht1aand5ht3receptorsattenuatesacuteandlongtermhypersensitivityassociatedwithneonatalproceduralpain
AT joostenelberta selectivetargetingofserotonin5ht1aand5ht3receptorsattenuatesacuteandlongtermhypersensitivityassociatedwithneonatalproceduralpain
AT patijnjacob selectivetargetingofserotonin5ht1aand5ht3receptorsattenuatesacuteandlongtermhypersensitivityassociatedwithneonatalproceduralpain
AT tibboeldick selectivetargetingofserotonin5ht1aand5ht3receptorsattenuatesacuteandlongtermhypersensitivityassociatedwithneonatalproceduralpain
AT vandenhoogennynkej selectivetargetingofserotonin5ht1aand5ht3receptorsattenuatesacuteandlongtermhypersensitivityassociatedwithneonatalproceduralpain