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Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury
Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267572/ https://www.ncbi.nlm.nih.gov/pubmed/34248674 http://dx.doi.org/10.3389/fphys.2021.687046 |
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author | Tao, Xueshu Luo, Xin Zhang, Tianhe Hershey, Brad Esteller, Rosana Ji, Ru-Rong |
author_facet | Tao, Xueshu Luo, Xin Zhang, Tianhe Hershey, Brad Esteller, Rosana Ji, Ru-Rong |
author_sort | Tao, Xueshu |
collection | PubMed |
description | Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and this stimulation alone was sufficient to effectively reduce nerve injury-induced mechanical allodynia during stimulation without affecting SNI-induced cold allodynia. SCS alone significantly reduced interleukin-1β levels in both serum and CSF samples. Strikingly, SCS significantly increased RvD1 levels in the CSF but not serum. Finally, intrathecal injection of RvD1 (100 and 500 ng, i.t.) 4 weeks after nerve injury reduced SNI-induced mechanical allodynia in a dose-dependent manner. Our findings suggest that 1 kHz SCS may alleviate neuropathic pain via reduction of IL-1β and via production and/or release of RvD1 to control SNI-induced neuroinflammation. |
format | Online Article Text |
id | pubmed-8267572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82675722021-07-10 Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury Tao, Xueshu Luo, Xin Zhang, Tianhe Hershey, Brad Esteller, Rosana Ji, Ru-Rong Front Physiol Physiology Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and this stimulation alone was sufficient to effectively reduce nerve injury-induced mechanical allodynia during stimulation without affecting SNI-induced cold allodynia. SCS alone significantly reduced interleukin-1β levels in both serum and CSF samples. Strikingly, SCS significantly increased RvD1 levels in the CSF but not serum. Finally, intrathecal injection of RvD1 (100 and 500 ng, i.t.) 4 weeks after nerve injury reduced SNI-induced mechanical allodynia in a dose-dependent manner. Our findings suggest that 1 kHz SCS may alleviate neuropathic pain via reduction of IL-1β and via production and/or release of RvD1 to control SNI-induced neuroinflammation. Frontiers Media S.A. 2021-06-25 /pmc/articles/PMC8267572/ /pubmed/34248674 http://dx.doi.org/10.3389/fphys.2021.687046 Text en Copyright © 2021 Tao, Luo, Zhang, Hershey, Esteller and Ji. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Tao, Xueshu Luo, Xin Zhang, Tianhe Hershey, Brad Esteller, Rosana Ji, Ru-Rong Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title | Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title_full | Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title_fullStr | Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title_full_unstemmed | Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title_short | Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury |
title_sort | spinal cord stimulation attenuates mechanical allodynia and increases central resolvin d1 levels in rats with spared nerve injury |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267572/ https://www.ncbi.nlm.nih.gov/pubmed/34248674 http://dx.doi.org/10.3389/fphys.2021.687046 |
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