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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...

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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
Descripción
Sumario: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.