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Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway

Repeat mild traumatic brain injuries (RmTBI) result in substantial burden to the public health system given their association with chronic post-injury pathologies, such as chronic pain and post-traumatic headache. Although this may relate to dysfunctional descending pain modulation (DPM), it is unce...

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Autores principales: Christensen, Jennaya, MacPherson, Naomi, Li, Crystal, Yamakawa, Glenn R., Mychasiuk, Richelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Milan 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268396/
https://www.ncbi.nlm.nih.gov/pubmed/37316796
http://dx.doi.org/10.1186/s10194-023-01608-y
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author Christensen, Jennaya
MacPherson, Naomi
Li, Crystal
Yamakawa, Glenn R.
Mychasiuk, Richelle
author_facet Christensen, Jennaya
MacPherson, Naomi
Li, Crystal
Yamakawa, Glenn R.
Mychasiuk, Richelle
author_sort Christensen, Jennaya
collection PubMed
description Repeat mild traumatic brain injuries (RmTBI) result in substantial burden to the public health system given their association with chronic post-injury pathologies, such as chronic pain and post-traumatic headache. Although this may relate to dysfunctional descending pain modulation (DPM), it is uncertain what mechanisms drive changes within this pathway. One possibility is altered orexinergic system functioning, as orexin is a potent anti-nociceptive neuromodulator. Orexin is exclusively produced by the lateral hypothalamus (LH) and receives excitatory innervation from the lateral parabrachial nucleus (lPBN). Therefore, we used neuronal tract-tracing to investigate the relationship between RmTBI and connectivity between lPBN and the LH, as well as orexinergic projections to a key site within the DPM, the periaqueductal gray (PAG). Prior to injury induction, retrograde and anterograde tract-tracing surgery was performed on 70 young-adult male Sprague Dawley rats, targeting the lPBN and PAG. Rodents were then randomly assigned to receive RmTBIs or sham injuries before undergoing testing for anxiety-like behaviour and nociceptive sensitivity. Immunohistochemical analysis identified distinct and co-localized orexin and tract-tracing cell bodies and projections within the LH. The RmTBI group exhibited altered nociception and reduced anxiety as well as a loss of orexin cell bodies and a reduction of hypothalamic projections to the ventrolateral nucleus of the PAG. However, there was no significant effect of injury on neuronal connectivity between the lPBN and orexinergic cell bodies within the LH. Our identification of structural losses and the resulting physiological changes in the orexinergic system following RmTBI begins to clarify acute post-injury mechanistic changes that drive may drive the development of post-traumatic headache and the chronification of pain.
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spelling pubmed-102683962023-06-15 Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway Christensen, Jennaya MacPherson, Naomi Li, Crystal Yamakawa, Glenn R. Mychasiuk, Richelle J Headache Pain Research Repeat mild traumatic brain injuries (RmTBI) result in substantial burden to the public health system given their association with chronic post-injury pathologies, such as chronic pain and post-traumatic headache. Although this may relate to dysfunctional descending pain modulation (DPM), it is uncertain what mechanisms drive changes within this pathway. One possibility is altered orexinergic system functioning, as orexin is a potent anti-nociceptive neuromodulator. Orexin is exclusively produced by the lateral hypothalamus (LH) and receives excitatory innervation from the lateral parabrachial nucleus (lPBN). Therefore, we used neuronal tract-tracing to investigate the relationship between RmTBI and connectivity between lPBN and the LH, as well as orexinergic projections to a key site within the DPM, the periaqueductal gray (PAG). Prior to injury induction, retrograde and anterograde tract-tracing surgery was performed on 70 young-adult male Sprague Dawley rats, targeting the lPBN and PAG. Rodents were then randomly assigned to receive RmTBIs or sham injuries before undergoing testing for anxiety-like behaviour and nociceptive sensitivity. Immunohistochemical analysis identified distinct and co-localized orexin and tract-tracing cell bodies and projections within the LH. The RmTBI group exhibited altered nociception and reduced anxiety as well as a loss of orexin cell bodies and a reduction of hypothalamic projections to the ventrolateral nucleus of the PAG. However, there was no significant effect of injury on neuronal connectivity between the lPBN and orexinergic cell bodies within the LH. Our identification of structural losses and the resulting physiological changes in the orexinergic system following RmTBI begins to clarify acute post-injury mechanistic changes that drive may drive the development of post-traumatic headache and the chronification of pain. Springer Milan 2023-06-14 /pmc/articles/PMC10268396/ /pubmed/37316796 http://dx.doi.org/10.1186/s10194-023-01608-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Christensen, Jennaya
MacPherson, Naomi
Li, Crystal
Yamakawa, Glenn R.
Mychasiuk, Richelle
Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title_full Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title_fullStr Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title_full_unstemmed Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title_short Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
title_sort repeat mild traumatic brain injuries (rmtbi) modify nociception and disrupt orexinergic connectivity within the descending pain pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268396/
https://www.ncbi.nlm.nih.gov/pubmed/37316796
http://dx.doi.org/10.1186/s10194-023-01608-y
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