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Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia
Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503748/ https://www.ncbi.nlm.nih.gov/pubmed/34608504 http://dx.doi.org/10.3892/mmr.2021.12475 |
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author | Wang, Jian Wu, Xiao-Chen Zhang, Ming-Ming Ren, Jia-Hao Sun, Yi Liu, Jing-Zhen Wu, Xi-Qiang He, Si-Yi Li, Yun-Qing Zhang, Jin-Bao |
author_facet | Wang, Jian Wu, Xiao-Chen Zhang, Ming-Ming Ren, Jia-Hao Sun, Yi Liu, Jing-Zhen Wu, Xi-Qiang He, Si-Yi Li, Yun-Qing Zhang, Jin-Bao |
author_sort | Wang, Jian |
collection | PubMed |
description | Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain-relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI-induced spinal dorsal horn microglial activation, with downregulation of ionized calcium-binding adaptor protein-1 expression. Moreover, SCS inhibited CMI-induced spinal expression of phosphorylated-p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI-induced IL-1β and TNF-α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia-activating factor) partially reversed the SCS-produced analgesic effects on CMI-induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS-produced analgesic effects on chronic cardiac pain. |
format | Online Article Text |
id | pubmed-8503748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-85037482021-10-19 Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia Wang, Jian Wu, Xiao-Chen Zhang, Ming-Ming Ren, Jia-Hao Sun, Yi Liu, Jing-Zhen Wu, Xi-Qiang He, Si-Yi Li, Yun-Qing Zhang, Jin-Bao Mol Med Rep Articles Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain-relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI-induced spinal dorsal horn microglial activation, with downregulation of ionized calcium-binding adaptor protein-1 expression. Moreover, SCS inhibited CMI-induced spinal expression of phosphorylated-p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI-induced IL-1β and TNF-α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia-activating factor) partially reversed the SCS-produced analgesic effects on CMI-induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS-produced analgesic effects on chronic cardiac pain. D.A. Spandidos 2021-12 2021-10-01 /pmc/articles/PMC8503748/ /pubmed/34608504 http://dx.doi.org/10.3892/mmr.2021.12475 Text en Copyright: © Wang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wang, Jian Wu, Xiao-Chen Zhang, Ming-Ming Ren, Jia-Hao Sun, Yi Liu, Jing-Zhen Wu, Xi-Qiang He, Si-Yi Li, Yun-Qing Zhang, Jin-Bao Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title | Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title_full | Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title_fullStr | Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title_full_unstemmed | Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title_short | Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
title_sort | spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503748/ https://www.ncbi.nlm.nih.gov/pubmed/34608504 http://dx.doi.org/10.3892/mmr.2021.12475 |
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