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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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8138 |
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| author | Ji Hwan Lee Jong Hee Choi Jaihwan Kim Tai Wan Kim Ji-Young Kim Geehoon Chung Ik-Hyun Cho Dae Sik Jang Sun Kwang Kim |
| author_facet | Ji Hwan Lee Jong Hee Choi Jaihwan Kim Tai Wan Kim Ji-Young Kim Geehoon Chung Ik-Hyun Cho Dae Sik Jang Sun Kwang Kim |
| author_sort | Ji Hwan Lee |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T17:40:50Z |
| format | Article |
| id | doaj.art-939b847a0e304d338eac3b4756d0f151 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:40:50Z |
| publishDate | 2022-11-01 |
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| series | Molecules |
| spelling | doaj.art-939b847a0e304d338eac3b4756d0f1512023-11-24T11:37:14ZengMDPI AGMolecules1420-30492022-11-012723813810.3390/molecules27238138Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal MicrogliaJi Hwan Lee0Jong Hee Choi1Jaihwan Kim2Tai Wan Kim3Ji-Young Kim4Geehoon Chung5Ik-Hyun Cho6Dae Sik Jang7Sun Kwang Kim8Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaOxaliplatin-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.https://www.mdpi.com/1420-3049/27/23/8138inflammationmicroglianeuropathic painoxaliplatinphytochemicalsyrinagresinol |
| spellingShingle | Ji Hwan Lee Jong Hee Choi Jaihwan Kim Tai Wan Kim Ji-Young Kim Geehoon Chung Ik-Hyun Cho Dae Sik Jang Sun Kwang Kim Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia Molecules inflammation microglia neuropathic pain oxaliplatin phytochemical syrinagresinol |
| 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 | inflammation microglia neuropathic pain oxaliplatin phytochemical syrinagresinol |
| url | https://www.mdpi.com/1420-3049/27/23/8138 |
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