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Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia

Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigat...

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Autores principales: Lee, Ji Hwan, Choi, Jong Hee, Kim, Jaihwan, Kim, Tai Wan, Kim, Ji-Young, Chung, Geehoon, Cho, Ik-Hyun, Jang, Dae Sik, Kim, Sun Kwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736412/
https://www.ncbi.nlm.nih.gov/pubmed/36500231
http://dx.doi.org/10.3390/molecules27238138
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author Lee, Ji Hwan
Choi, Jong Hee
Kim, Jaihwan
Kim, Tai Wan
Kim, Ji-Young
Chung, Geehoon
Cho, Ik-Hyun
Jang, Dae Sik
Kim, Sun Kwang
author_facet Lee, Ji Hwan
Choi, Jong Hee
Kim, Jaihwan
Kim, Tai Wan
Kim, Ji-Young
Chung, Geehoon
Cho, Ik-Hyun
Jang, Dae Sik
Kim, Sun Kwang
author_sort Lee, Ji Hwan
collection PubMed
description Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigate the causal relationship between spinal microglial activation and OIPN and explore the analgesic effects of syringaresinol, a phytochemical from the bark of Cinnamomum cassia, on OIPN symptoms. The causality between microglial activation and OIPN was investigated by assessing cold and mechanical allodynia in mice after intrathecal injection of the serum supernatant from a BV-2 microglial cell line treated with oxaliplatin. The microglial inflammatory response was measured based on inducible nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated nuclear factor-kappa B (p-NF-κB) expression in the spinal dorsal horn. The effects of syringaresinol were tested using behavioral and immunohistochemical assays. We found that oxaliplatin treatment activated the microglia to increase inflammatory responses, leading to the induction of pain. Syringaresinol treatment significantly ameliorated oxaliplatin-induced pain and suppressed microglial expression of inflammatory signaling molecules. Thus, we concluded that the analgesic effects of syringaresinol on OIPN were achieved via the modulation of spinal microglial inflammatory responses.
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spelling pubmed-97364122022-12-11 Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia Lee, Ji Hwan Choi, Jong Hee Kim, Jaihwan Kim, Tai Wan Kim, Ji-Young Chung, Geehoon Cho, Ik-Hyun Jang, Dae Sik Kim, Sun Kwang Molecules Article Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigate the causal relationship between spinal microglial activation and OIPN and explore the analgesic effects of syringaresinol, a phytochemical from the bark of Cinnamomum cassia, on OIPN symptoms. The causality between microglial activation and OIPN was investigated by assessing cold and mechanical allodynia in mice after intrathecal injection of the serum supernatant from a BV-2 microglial cell line treated with oxaliplatin. The microglial inflammatory response was measured based on inducible nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated nuclear factor-kappa B (p-NF-κB) expression in the spinal dorsal horn. The effects of syringaresinol were tested using behavioral and immunohistochemical assays. We found that oxaliplatin treatment activated the microglia to increase inflammatory responses, leading to the induction of pain. Syringaresinol treatment significantly ameliorated oxaliplatin-induced pain and suppressed microglial expression of inflammatory signaling molecules. Thus, we concluded that the analgesic effects of syringaresinol on OIPN were achieved via the modulation of spinal microglial inflammatory responses. MDPI 2022-11-23 /pmc/articles/PMC9736412/ /pubmed/36500231 http://dx.doi.org/10.3390/molecules27238138 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Ji Hwan
Choi, Jong Hee
Kim, Jaihwan
Kim, Tai Wan
Kim, Ji-Young
Chung, Geehoon
Cho, Ik-Hyun
Jang, Dae Sik
Kim, Sun Kwang
Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title_full Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title_fullStr Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title_full_unstemmed Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title_short Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia
title_sort syringaresinol alleviates oxaliplatin-induced neuropathic pain symptoms by inhibiting the inflammatory responses of spinal microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736412/
https://www.ncbi.nlm.nih.gov/pubmed/36500231
http://dx.doi.org/10.3390/molecules27238138
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