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Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation
High rates of acute and chronic pain are associated with traumatic brain injury (TBI), but mechanisms responsible for the association remain elusive. Recent data suggest dysregulated descending pain modulation circuitry could be involved. Based on these and other observations, we hypothesized that s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925232/ https://www.ncbi.nlm.nih.gov/pubmed/31863005 http://dx.doi.org/10.1038/s41598-019-55739-x |
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author | Sahbaie, Peyman Irvine, Karen-Amanda Liang, De-Yong Shi, Xiaoyou Clark, J. David |
author_facet | Sahbaie, Peyman Irvine, Karen-Amanda Liang, De-Yong Shi, Xiaoyou Clark, J. David |
author_sort | Sahbaie, Peyman |
collection | PubMed |
description | High rates of acute and chronic pain are associated with traumatic brain injury (TBI), but mechanisms responsible for the association remain elusive. Recent data suggest dysregulated descending pain modulation circuitry could be involved. Based on these and other observations, we hypothesized that serotonin (5-HT)-dependent activation of spinal CXC Motif Chemokine Receptor 2 (CXCR2) may support TBI-related nociceptive sensitization in a mouse model of mild TBI (mTBI). We observed that systemic 5-HT depletion with p-chlorophenylalanine attenuated mechanical hypersensitivity seen after mTBI. Likewise, selective spinal 5-HT fiber depletion with 5,7-dihydroxytryptamine (5,7-DHT) reduced hypersensitivity after mTBI. Consistent with a role for spinal 5-HT(3) serotonin receptors, intrathecal ondansetron administration after TBI dose-dependently attenuated nociceptive sensitization. Also, selective CXCR2 antagonist SCH527123 treatment attenuated mechanical hypersensitivity after mTBI. Furthermore, spinal CXCL1 and CXCL2 mRNA and protein levels were increased after mTBI as were GFAP and IBA-1 markers. Spinal 5,7-DHT application reduced both chemokine expression and glial activation. Our results suggest dual pathways for nociceptive sensitization after mTBI, direct 5-HT effect through 5-HT(3) receptors and indirectly through upregulation of chemokine signaling. Designing novel clinical interventions against either the 5-HT(3) mediated component or chemokine pathway may be beneficial in treating pain frequently seen in patients after mTBI. |
format | Online Article Text |
id | pubmed-6925232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69252322019-12-24 Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation Sahbaie, Peyman Irvine, Karen-Amanda Liang, De-Yong Shi, Xiaoyou Clark, J. David Sci Rep Article High rates of acute and chronic pain are associated with traumatic brain injury (TBI), but mechanisms responsible for the association remain elusive. Recent data suggest dysregulated descending pain modulation circuitry could be involved. Based on these and other observations, we hypothesized that serotonin (5-HT)-dependent activation of spinal CXC Motif Chemokine Receptor 2 (CXCR2) may support TBI-related nociceptive sensitization in a mouse model of mild TBI (mTBI). We observed that systemic 5-HT depletion with p-chlorophenylalanine attenuated mechanical hypersensitivity seen after mTBI. Likewise, selective spinal 5-HT fiber depletion with 5,7-dihydroxytryptamine (5,7-DHT) reduced hypersensitivity after mTBI. Consistent with a role for spinal 5-HT(3) serotonin receptors, intrathecal ondansetron administration after TBI dose-dependently attenuated nociceptive sensitization. Also, selective CXCR2 antagonist SCH527123 treatment attenuated mechanical hypersensitivity after mTBI. Furthermore, spinal CXCL1 and CXCL2 mRNA and protein levels were increased after mTBI as were GFAP and IBA-1 markers. Spinal 5,7-DHT application reduced both chemokine expression and glial activation. Our results suggest dual pathways for nociceptive sensitization after mTBI, direct 5-HT effect through 5-HT(3) receptors and indirectly through upregulation of chemokine signaling. Designing novel clinical interventions against either the 5-HT(3) mediated component or chemokine pathway may be beneficial in treating pain frequently seen in patients after mTBI. Nature Publishing Group UK 2019-12-20 /pmc/articles/PMC6925232/ /pubmed/31863005 http://dx.doi.org/10.1038/s41598-019-55739-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Sahbaie, Peyman Irvine, Karen-Amanda Liang, De-Yong Shi, Xiaoyou Clark, J. David Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title | Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title_full | Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title_fullStr | Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title_full_unstemmed | Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title_short | Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation |
title_sort | mild traumatic brain injury causes nociceptive sensitization through spinal chemokine upregulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925232/ https://www.ncbi.nlm.nih.gov/pubmed/31863005 http://dx.doi.org/10.1038/s41598-019-55739-x |
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