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Forebrain medial septum sustains experimental neuropathic pain

The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of c...

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Autores principales: Ariffin, Mohammed Zacky, Ibrahim, Khairunisa Mohamad, Lee, Andy Thiam-Huat, Lee, Rui Zhi, Poon, Shou Yu, Thong, Hwai Kit, Liu, Eugene Hern Choon, Low, Chian-Ming, Khanna, Sanjay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082830/
https://www.ncbi.nlm.nih.gov/pubmed/30089875
http://dx.doi.org/10.1038/s41598-018-30177-3
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author Ariffin, Mohammed Zacky
Ibrahim, Khairunisa Mohamad
Lee, Andy Thiam-Huat
Lee, Rui Zhi
Poon, Shou Yu
Thong, Hwai Kit
Liu, Eugene Hern Choon
Low, Chian-Ming
Khanna, Sanjay
author_facet Ariffin, Mohammed Zacky
Ibrahim, Khairunisa Mohamad
Lee, Andy Thiam-Huat
Lee, Rui Zhi
Poon, Shou Yu
Thong, Hwai Kit
Liu, Eugene Hern Choon
Low, Chian-Ming
Khanna, Sanjay
author_sort Ariffin, Mohammed Zacky
collection PubMed
description The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of chemotherapy-induced neuropathic pain. For example, inactivation of the MS with intraseptal muscimol (2 μg/μl, 0.5 μl), a GABA mimetic, reversed peripheral hypersensitivity (PH) in the CCI model and induced place preference in a conditioned place preference task, a surrogate measure of spontaneous nociception. The effect of intraseptal muscimol on PH was comparable to that seen with microinjection of the local anesthetic, lidocaine, into rostral ventromedial medulla which is implicated in facilitating experimental chronic nociception. Cellular analysis in the CCI model showed that the MS region sustains nociceptive gain with CCI by facilitating basal nociceptive processing and the amplification of stimulus-evoked neural processing. Indeed, consistent with the idea that excitatory transmission through MS facilitates chronic experimental pain, intraseptal microinjection of antagonists acting at AMPA and NMDA glutamate receptors attenuated CCI-induced PH. We propose that the MS is a central monitor of bodily nociception which sustains molecular plasticity triggered by persistent noxious insult.
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spelling pubmed-60828302018-08-10 Forebrain medial septum sustains experimental neuropathic pain Ariffin, Mohammed Zacky Ibrahim, Khairunisa Mohamad Lee, Andy Thiam-Huat Lee, Rui Zhi Poon, Shou Yu Thong, Hwai Kit Liu, Eugene Hern Choon Low, Chian-Ming Khanna, Sanjay Sci Rep Article The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of chemotherapy-induced neuropathic pain. For example, inactivation of the MS with intraseptal muscimol (2 μg/μl, 0.5 μl), a GABA mimetic, reversed peripheral hypersensitivity (PH) in the CCI model and induced place preference in a conditioned place preference task, a surrogate measure of spontaneous nociception. The effect of intraseptal muscimol on PH was comparable to that seen with microinjection of the local anesthetic, lidocaine, into rostral ventromedial medulla which is implicated in facilitating experimental chronic nociception. Cellular analysis in the CCI model showed that the MS region sustains nociceptive gain with CCI by facilitating basal nociceptive processing and the amplification of stimulus-evoked neural processing. Indeed, consistent with the idea that excitatory transmission through MS facilitates chronic experimental pain, intraseptal microinjection of antagonists acting at AMPA and NMDA glutamate receptors attenuated CCI-induced PH. We propose that the MS is a central monitor of bodily nociception which sustains molecular plasticity triggered by persistent noxious insult. Nature Publishing Group UK 2018-08-08 /pmc/articles/PMC6082830/ /pubmed/30089875 http://dx.doi.org/10.1038/s41598-018-30177-3 Text en © The Author(s) 2018 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
Ariffin, Mohammed Zacky
Ibrahim, Khairunisa Mohamad
Lee, Andy Thiam-Huat
Lee, Rui Zhi
Poon, Shou Yu
Thong, Hwai Kit
Liu, Eugene Hern Choon
Low, Chian-Ming
Khanna, Sanjay
Forebrain medial septum sustains experimental neuropathic pain
title Forebrain medial septum sustains experimental neuropathic pain
title_full Forebrain medial septum sustains experimental neuropathic pain
title_fullStr Forebrain medial septum sustains experimental neuropathic pain
title_full_unstemmed Forebrain medial septum sustains experimental neuropathic pain
title_short Forebrain medial septum sustains experimental neuropathic pain
title_sort forebrain medial septum sustains experimental neuropathic pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082830/
https://www.ncbi.nlm.nih.gov/pubmed/30089875
http://dx.doi.org/10.1038/s41598-018-30177-3
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