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Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain
BACKGROUND: The mechanisms by which painful injuries are linked to the multitude of pain-related comorbidities and neuroplastic changes in the brain remain poorly understood. Here we propose a model that relies on epi-neuronal communication through the vascular system to effect various brain structu...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600335/ https://www.ncbi.nlm.nih.gov/pubmed/26453186 http://dx.doi.org/10.1186/s12990-015-0066-6 |
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author | Tajerian, Maral Clark, J. David |
author_facet | Tajerian, Maral Clark, J. David |
author_sort | Tajerian, Maral |
collection | PubMed |
description | BACKGROUND: The mechanisms by which painful injuries are linked to the multitude of pain-related comorbidities and neuroplastic changes in the brain remain poorly understood. Here we propose a model that relies on epi-neuronal communication through the vascular system to effect various brain structures. Specifically, we hypothesize that the differential vulnerability of the blood–brain barrier (BBB) in different brain regions is associated with region-specific neuroplastic and neurovascular changes that are in turn associated with particular pain-related comorbidities. PRESENTATION OF THE HYPOTHESIS: We will present our hypothesis by focusing on two main points: (A) chronic pain (CP) is associated with differential BBB compromise. (B) Circulating mediators leaking through the BBB create cytogenic and neovascular niches associated with pain-related co-morbidities. TESTING THE HYPOTHESIS: Pre-clinically, our hypothesis can be tested by observing, in parallel, BBB compromise, (neo)vascularization, neurogenesis, and their co-localization in animal pain models using imaging, microscopy, biochemical and other tools. Furthermore, the BBB can be experimentally damaged in specific brain regions, and the consequences of those lesions studied on nociception and associated comorbidities. Recently developed imaging techniques allow the analysis of blood brain barrier integrity in patients providing a route for translation of the laboratory findings. Though perhaps more limited, post-mortem examination of brains with available pain histories constitutes a second approach to addressing this hypothesis. IMPLICATIONS OF THE HYPOTHESIS: Understanding changes in BBB permeability in chronic pain conditions has clear implications both for understanding the pathogenesis of chronic pain and for the design of novel treatments to prevent chronic pain and its consequences. More broadly, this hypothesis may help us to understand how peripheral injuries impact the brain via mechanisms other than commonly studied efferent sensory pathways. |
format | Online Article Text |
id | pubmed-4600335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46003352015-10-11 Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain Tajerian, Maral Clark, J. David Mol Pain Hypothesis BACKGROUND: The mechanisms by which painful injuries are linked to the multitude of pain-related comorbidities and neuroplastic changes in the brain remain poorly understood. Here we propose a model that relies on epi-neuronal communication through the vascular system to effect various brain structures. Specifically, we hypothesize that the differential vulnerability of the blood–brain barrier (BBB) in different brain regions is associated with region-specific neuroplastic and neurovascular changes that are in turn associated with particular pain-related comorbidities. PRESENTATION OF THE HYPOTHESIS: We will present our hypothesis by focusing on two main points: (A) chronic pain (CP) is associated with differential BBB compromise. (B) Circulating mediators leaking through the BBB create cytogenic and neovascular niches associated with pain-related co-morbidities. TESTING THE HYPOTHESIS: Pre-clinically, our hypothesis can be tested by observing, in parallel, BBB compromise, (neo)vascularization, neurogenesis, and their co-localization in animal pain models using imaging, microscopy, biochemical and other tools. Furthermore, the BBB can be experimentally damaged in specific brain regions, and the consequences of those lesions studied on nociception and associated comorbidities. Recently developed imaging techniques allow the analysis of blood brain barrier integrity in patients providing a route for translation of the laboratory findings. Though perhaps more limited, post-mortem examination of brains with available pain histories constitutes a second approach to addressing this hypothesis. IMPLICATIONS OF THE HYPOTHESIS: Understanding changes in BBB permeability in chronic pain conditions has clear implications both for understanding the pathogenesis of chronic pain and for the design of novel treatments to prevent chronic pain and its consequences. More broadly, this hypothesis may help us to understand how peripheral injuries impact the brain via mechanisms other than commonly studied efferent sensory pathways. BioMed Central 2015-10-09 /pmc/articles/PMC4600335/ /pubmed/26453186 http://dx.doi.org/10.1186/s12990-015-0066-6 Text en © Tajerian and Clark. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Hypothesis Tajerian, Maral Clark, J. David Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title | Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title_full | Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title_fullStr | Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title_full_unstemmed | Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title_short | Novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
title_sort | novel cytogenic and neurovascular niches due to blood–brain barrier compromise in the chronic pain brain |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600335/ https://www.ncbi.nlm.nih.gov/pubmed/26453186 http://dx.doi.org/10.1186/s12990-015-0066-6 |
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