Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury
BackgroundNeuropathic pain (NP) is one of intractable complications of spinal cord injury (SCI) and lacks effective treatment. Resveratrol (Res) has been shown to possess potent anti-inflammatory and anti-nociceptive effects. In this study, we investigated the analgesic effect of Res and its underly...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116679/full |
| _version_ | 1828014500244094976 |
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| author | Jie Han Zhen Hua Wen-jie Yang Shu Wang Fang Yan Jun-nan Wang Tao Sun |
| author_facet | Jie Han Zhen Hua Wen-jie Yang Shu Wang Fang Yan Jun-nan Wang Tao Sun |
| author_sort | Jie Han |
| collection | DOAJ |
| description | BackgroundNeuropathic pain (NP) is one of intractable complications of spinal cord injury (SCI) and lacks effective treatment. Resveratrol (Res) has been shown to possess potent anti-inflammatory and anti-nociceptive effects. In this study, we investigated the analgesic effect of Res and its underlying mechanism in a rat model of SCI.MethodsThe rat thoracic (T10) spinal cord contusion injury model was established, and mechanical thresholds were evaluated during an observation period of 21 days. Intrathecal administration with Res (300 μg/10 μl) was performed once a day for 7 days after the operation. On postoperative day 7, the expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) and Real-time quantitative PCR (RT-qPCR), the expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was determined by western blot and RT-qPCR, and the co-labeled phospho-STAT3 (p-STAT3) with neuronal nuclear antigen (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba-1) were explored by double immunofluorescence staining in the lumbar spinal dorsal horns. The temporal changes of p-STAT3 were investigated by western blot on the 1st, 3rd, 7th, 14th, and 21st days after the operation.ResultsIntrathecal administration with Res for 7 successive days alleviated mechanical allodynia of rats during the observation period. Meanwhile, treatment with Res suppressed the production of pro-inflammatory factors TNF-α, IL-1β and IL-6, and inhibited the expressions of phospho-JAK2 and p-STAT3 in the lumbar spinal dorsal horns on postoperative day 7. Additionally, the protein expression of p-STAT3 was significantly increased on the 1st day following the operation and remained elevated during the next 21 days, immunofluorescence suggested that the up-regulated p-STAT3 was co-located with glial cells and neurons.ConclusionOur current results indicated that intrathecal administration with Res effectively alleviated mechanical allodynia after SCI in rats, and its analgesic mechanism might be to suppress neuroinflammation by partly inhibiting JAK2/STAT3 signaling pathway. |
| first_indexed | 2024-04-10T10:03:08Z |
| format | Article |
| id | doaj.art-4a22389d02a441a0bfbab376b60ccd94 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-10T10:03:08Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-4a22389d02a441a0bfbab376b60ccd942023-02-16T05:19:54ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-02-011610.3389/fnmol.2023.11166791116679Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injuryJie Han0Zhen Hua1Wen-jie Yang2Shu Wang3Fang Yan4Jun-nan Wang5Tao Sun6Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaCollege of Sports Medicines and Rehabilitation, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai’an, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaBackgroundNeuropathic pain (NP) is one of intractable complications of spinal cord injury (SCI) and lacks effective treatment. Resveratrol (Res) has been shown to possess potent anti-inflammatory and anti-nociceptive effects. In this study, we investigated the analgesic effect of Res and its underlying mechanism in a rat model of SCI.MethodsThe rat thoracic (T10) spinal cord contusion injury model was established, and mechanical thresholds were evaluated during an observation period of 21 days. Intrathecal administration with Res (300 μg/10 μl) was performed once a day for 7 days after the operation. On postoperative day 7, the expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) and Real-time quantitative PCR (RT-qPCR), the expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was determined by western blot and RT-qPCR, and the co-labeled phospho-STAT3 (p-STAT3) with neuronal nuclear antigen (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba-1) were explored by double immunofluorescence staining in the lumbar spinal dorsal horns. The temporal changes of p-STAT3 were investigated by western blot on the 1st, 3rd, 7th, 14th, and 21st days after the operation.ResultsIntrathecal administration with Res for 7 successive days alleviated mechanical allodynia of rats during the observation period. Meanwhile, treatment with Res suppressed the production of pro-inflammatory factors TNF-α, IL-1β and IL-6, and inhibited the expressions of phospho-JAK2 and p-STAT3 in the lumbar spinal dorsal horns on postoperative day 7. Additionally, the protein expression of p-STAT3 was significantly increased on the 1st day following the operation and remained elevated during the next 21 days, immunofluorescence suggested that the up-regulated p-STAT3 was co-located with glial cells and neurons.ConclusionOur current results indicated that intrathecal administration with Res effectively alleviated mechanical allodynia after SCI in rats, and its analgesic mechanism might be to suppress neuroinflammation by partly inhibiting JAK2/STAT3 signaling pathway.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116679/fullneuropathic painspinal cord injuryresveratrolJanus kinase 2/signal transducer and activator of transcription 3neuroinflammation |
| spellingShingle | Jie Han Zhen Hua Wen-jie Yang Shu Wang Fang Yan Jun-nan Wang Tao Sun Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury Frontiers in Molecular Neuroscience neuropathic pain spinal cord injury resveratrol Janus kinase 2/signal transducer and activator of transcription 3 neuroinflammation |
| title | Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| title_full | Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| title_fullStr | Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| title_full_unstemmed | Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| title_short | Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| title_sort | resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting janus kinase 2 signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury |
| topic | neuropathic pain spinal cord injury resveratrol Janus kinase 2/signal transducer and activator of transcription 3 neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116679/full |
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