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Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain
Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse side effect of many anti-cancer chemotherapeutic treatments. CIPN often causes neuropathic pain in extremities, and oxidative stress has been shown to be a major contributing factor to this pain. In this study, we determined the site of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458664/ https://www.ncbi.nlm.nih.gov/pubmed/30857460 http://dx.doi.org/10.1177/1744806919840098 |
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author | Shim, Hyun Soo Bae, Chilman Wang, Jigong Lee, Kyung-Hee Hankerd, Kali M Kim, Hee Kee Chung, Jin Mo La, Jun-Ho |
author_facet | Shim, Hyun Soo Bae, Chilman Wang, Jigong Lee, Kyung-Hee Hankerd, Kali M Kim, Hee Kee Chung, Jin Mo La, Jun-Ho |
author_sort | Shim, Hyun Soo |
collection | PubMed |
description | Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse side effect of many anti-cancer chemotherapeutic treatments. CIPN often causes neuropathic pain in extremities, and oxidative stress has been shown to be a major contributing factor to this pain. In this study, we determined the site of oxidative stress associated with pain (specifically, mechanical hypersensitivity) in cisplatin- and paclitaxel-treated mouse models of CIPN and investigated the neurophysiological mechanisms accounting for the pain. C57BL/6N mice that received either cisplatin or paclitaxel (2 mg/kg, once daily on four alternate days) developed mechanical hypersensitivity to von Frey filament stimulations of their hindpaws. Cisplatin-induced mechanical hypersensitivity was inhibited by silencing of Transient Receptor Potential channels V1 (TRPV1)- or TRPA1-expressing afferents, whereas paclitaxel-induced mechanical hypersensitivity was attenuated by silencing of Aβ fibers. Although systemic delivery of phenyl N-tert-butylnitrone, a reactive oxygen species scavenger, alleviated mechanical hypersensitivity in both cisplatin- and paclitaxel-treated mice, intraplantar phenyl N-tert-butylnitrone was effective only in cisplatin-treated mice, and intrathecal phenyl N-tert-butylnitrone, only in paclitaxel-treated mice. In a reactive oxygen species-dependent manner, the mechanosensitivity of Aδ/C fiber endings in the hindpaw skin was increased in cisplatin-treated mice, and the excitatory synaptic strength in the spinal dorsal horn was potentiated in paclitaxel-treated mice. Collectively, these results suggest that cisplatin-induced mechanical hypersensitivity is attributed to peripheral oxidative stress sensitizing mechanical nociceptors, whereas paclitaxel-induced mechanical hypersensitivity is due to central (spinal) oxidative stress maintaining central sensitization that abnormally produces pain in response to Aβ fiber inputs. |
format | Online Article Text |
id | pubmed-6458664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-64586642019-04-19 Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain Shim, Hyun Soo Bae, Chilman Wang, Jigong Lee, Kyung-Hee Hankerd, Kali M Kim, Hee Kee Chung, Jin Mo La, Jun-Ho Mol Pain Research Article Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse side effect of many anti-cancer chemotherapeutic treatments. CIPN often causes neuropathic pain in extremities, and oxidative stress has been shown to be a major contributing factor to this pain. In this study, we determined the site of oxidative stress associated with pain (specifically, mechanical hypersensitivity) in cisplatin- and paclitaxel-treated mouse models of CIPN and investigated the neurophysiological mechanisms accounting for the pain. C57BL/6N mice that received either cisplatin or paclitaxel (2 mg/kg, once daily on four alternate days) developed mechanical hypersensitivity to von Frey filament stimulations of their hindpaws. Cisplatin-induced mechanical hypersensitivity was inhibited by silencing of Transient Receptor Potential channels V1 (TRPV1)- or TRPA1-expressing afferents, whereas paclitaxel-induced mechanical hypersensitivity was attenuated by silencing of Aβ fibers. Although systemic delivery of phenyl N-tert-butylnitrone, a reactive oxygen species scavenger, alleviated mechanical hypersensitivity in both cisplatin- and paclitaxel-treated mice, intraplantar phenyl N-tert-butylnitrone was effective only in cisplatin-treated mice, and intrathecal phenyl N-tert-butylnitrone, only in paclitaxel-treated mice. In a reactive oxygen species-dependent manner, the mechanosensitivity of Aδ/C fiber endings in the hindpaw skin was increased in cisplatin-treated mice, and the excitatory synaptic strength in the spinal dorsal horn was potentiated in paclitaxel-treated mice. Collectively, these results suggest that cisplatin-induced mechanical hypersensitivity is attributed to peripheral oxidative stress sensitizing mechanical nociceptors, whereas paclitaxel-induced mechanical hypersensitivity is due to central (spinal) oxidative stress maintaining central sensitization that abnormally produces pain in response to Aβ fiber inputs. SAGE Publications 2019-04-10 /pmc/articles/PMC6458664/ /pubmed/30857460 http://dx.doi.org/10.1177/1744806919840098 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Shim, Hyun Soo Bae, Chilman Wang, Jigong Lee, Kyung-Hee Hankerd, Kali M Kim, Hee Kee Chung, Jin Mo La, Jun-Ho Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title | Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title_full | Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title_fullStr | Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title_full_unstemmed | Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title_short | Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
title_sort | peripheral and central oxidative stress in chemotherapy-induced neuropathic pain |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458664/ https://www.ncbi.nlm.nih.gov/pubmed/30857460 http://dx.doi.org/10.1177/1744806919840098 |
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