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Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors
The loss of diffuse noxious inhibitory controls (DNIC) is recognized as a predictor of chronic pain. Mechanistically, DNIC produces analgesia by a heterotopically applied conditioning-noxious stimulus (CS) and yet underexplored descending modulatory inputs. Here, we aimed at studying DNIC in monoart...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006856/ https://www.ncbi.nlm.nih.gov/pubmed/36915290 http://dx.doi.org/10.1016/j.ynpai.2023.100123 |
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author | Pereira-Silva, Raquel Serrão, Paula Lourença Neto, Fani Martins, Isabel |
author_facet | Pereira-Silva, Raquel Serrão, Paula Lourença Neto, Fani Martins, Isabel |
author_sort | Pereira-Silva, Raquel |
collection | PubMed |
description | The loss of diffuse noxious inhibitory controls (DNIC) is recognized as a predictor of chronic pain. Mechanistically, DNIC produces analgesia by a heterotopically applied conditioning-noxious stimulus (CS) and yet underexplored descending modulatory inputs. Here, we aimed at studying DNIC in monoarthritis (MA) by exploring the spinal component of the descending serotonergic system, specifically 5-hydroxytryptamine 3 receptors (5-HT3R). MA was induced in male Wistar rats by tibiotarsal injection of complete Freund’s adjuvant. Mechanical hyperalgesia and DNIC were assessed weekly by the Randall-Selitto test. Immunohistochemistry was used to quantify spinal 5-HT3R, and tryptophan hydroxylase (TPH) colocalization with phosphorylated extracellular signal-regulated protein kinases 1/2 at the rostroventromedial medulla (RVM). Spinal serotonin (5-HT) was quantified by HPLC. The effects of intrathecal ondansetron, a 5-HT3R antagonist, were assessed on mechanical hyperalgesia and DNIC. MA resulted in a prolonged steady-state mechanical hyperalgesia. In contrast, DNIC peaked after 28 days, decreasing afterwards until extinction at 42 days. At this later timepoint, MA rats showed increased: (i) spinal 5-HT3R and 5-HT levels, (ii) neuronal serotonergic activation and TPH expression at the RVM. Ondansetron reversed mechanical hyperalgesia and restored DNIC, regardless of being administered before or after CS. However, data variability was higher upon administration before CS in MA-animals. Prolonged MA upregulates the descending serotonergic modulation, which simultaneously results in increased nociception and DNIC extinction, through 5-HT3R. Our data suggest a role for spinal 5-HT3R in the top-down modulation of DNIC. Additionally, these receptors may also be involved in the bottom-up circuitry implicated in the trigger of DNIC. |
format | Online Article Text |
id | pubmed-10006856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100068562023-03-12 Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors Pereira-Silva, Raquel Serrão, Paula Lourença Neto, Fani Martins, Isabel Neurobiol Pain Original Research Article The loss of diffuse noxious inhibitory controls (DNIC) is recognized as a predictor of chronic pain. Mechanistically, DNIC produces analgesia by a heterotopically applied conditioning-noxious stimulus (CS) and yet underexplored descending modulatory inputs. Here, we aimed at studying DNIC in monoarthritis (MA) by exploring the spinal component of the descending serotonergic system, specifically 5-hydroxytryptamine 3 receptors (5-HT3R). MA was induced in male Wistar rats by tibiotarsal injection of complete Freund’s adjuvant. Mechanical hyperalgesia and DNIC were assessed weekly by the Randall-Selitto test. Immunohistochemistry was used to quantify spinal 5-HT3R, and tryptophan hydroxylase (TPH) colocalization with phosphorylated extracellular signal-regulated protein kinases 1/2 at the rostroventromedial medulla (RVM). Spinal serotonin (5-HT) was quantified by HPLC. The effects of intrathecal ondansetron, a 5-HT3R antagonist, were assessed on mechanical hyperalgesia and DNIC. MA resulted in a prolonged steady-state mechanical hyperalgesia. In contrast, DNIC peaked after 28 days, decreasing afterwards until extinction at 42 days. At this later timepoint, MA rats showed increased: (i) spinal 5-HT3R and 5-HT levels, (ii) neuronal serotonergic activation and TPH expression at the RVM. Ondansetron reversed mechanical hyperalgesia and restored DNIC, regardless of being administered before or after CS. However, data variability was higher upon administration before CS in MA-animals. Prolonged MA upregulates the descending serotonergic modulation, which simultaneously results in increased nociception and DNIC extinction, through 5-HT3R. Our data suggest a role for spinal 5-HT3R in the top-down modulation of DNIC. Additionally, these receptors may also be involved in the bottom-up circuitry implicated in the trigger of DNIC. Elsevier 2023-03-01 /pmc/articles/PMC10006856/ /pubmed/36915290 http://dx.doi.org/10.1016/j.ynpai.2023.100123 Text en © 2023 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Article Pereira-Silva, Raquel Serrão, Paula Lourença Neto, Fani Martins, Isabel Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title | Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title_full | Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title_fullStr | Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title_full_unstemmed | Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title_short | Diffuse noxious inhibitory controls in chronic joint inflammatory Pain: Study of the descending serotonergic modulation mediated through 5HT3 receptors |
title_sort | diffuse noxious inhibitory controls in chronic joint inflammatory pain: study of the descending serotonergic modulation mediated through 5ht3 receptors |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006856/ https://www.ncbi.nlm.nih.gov/pubmed/36915290 http://dx.doi.org/10.1016/j.ynpai.2023.100123 |
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