Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn
The exact mechanism underlies the development of neuropathic pain is not yet completely understood. Mitogen and stress-activated kinase 1 (MSK-1) is an important downstream kinase of the mitogen-activated protein kinase (MAPK). It has been extensively studied in the central nervous system, but wheth...
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Elsevier
2024-12-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024002697 |
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| author | Li Wang Yan Gao Yiming Qiao Xueli Wang Zongyi Liang Ji-Tian Xu Liren Li |
| author_facet | Li Wang Yan Gao Yiming Qiao Xueli Wang Zongyi Liang Ji-Tian Xu Liren Li |
| author_sort | Li Wang |
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| description | The exact mechanism underlies the development of neuropathic pain is not yet completely understood. Mitogen and stress-activated kinase 1 (MSK-1) is an important downstream kinase of the mitogen-activated protein kinase (MAPK). It has been extensively studied in the central nervous system, but whether MSK-1 is associated with the neuropathic pain remains elusive. In this experiment, Lumbar 5 spinal nerve ligation (SNL) was used to establish a neuropathic pain condition in the rats. Western blotting, qRT-PCR, immunohistochemistry, intrathecal catheterization and drugs delivery were evaluated to study the physiological responses of the animals. The results showed that SNL resulted in elevated phosphorylated MSK-1 (p-MSK-1) expression in the ipsilateral dorsal root ganglion (DRG) and the spinal dorsal horn in rats, while total MSK-1 (t-MSK-1) did not change significantly. Intrathecal injection of the MSK-1 inhibitor SB747651A partially reversed established neuropathic pain. Additionally, intrathecal administration of MSK-1 siRNA either preoperatively or 7 days postoperatively relieves the development and maintenance of pain, respectively. Meanwhile, the expression levels of p-H3S10, a downstream target of MSK-1, also displayed a significant increase after SNL. And these changes could be reversed by using MSK-1 siRNA. Collectively, the increase of MSK-1 induced by SNL participates in the development and maintenance of neuropathic pain by regulating the expression of p-H3S10 in DRG and spinal dorsal horn. Concentrating on MSK-1 may result in a novel approach to the treatment of neuropathic pain. |
| format | Article |
| id | doaj-art-58c46a0d36fb4d85a636b2c9afbca859 |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-58c46a0d36fb4d85a636b2c9afbca8592024-11-28T04:34:08ZengElsevierBrain Research Bulletin1873-27472024-12-01219111135Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal hornLi Wang0Yan Gao1Yiming Qiao2Xueli Wang3Zongyi Liang4Ji-Tian Xu5Liren Li6Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China; Neuroscience Research Institute, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, ChinaDepartment of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China; Corresponding author.The exact mechanism underlies the development of neuropathic pain is not yet completely understood. Mitogen and stress-activated kinase 1 (MSK-1) is an important downstream kinase of the mitogen-activated protein kinase (MAPK). It has been extensively studied in the central nervous system, but whether MSK-1 is associated with the neuropathic pain remains elusive. In this experiment, Lumbar 5 spinal nerve ligation (SNL) was used to establish a neuropathic pain condition in the rats. Western blotting, qRT-PCR, immunohistochemistry, intrathecal catheterization and drugs delivery were evaluated to study the physiological responses of the animals. The results showed that SNL resulted in elevated phosphorylated MSK-1 (p-MSK-1) expression in the ipsilateral dorsal root ganglion (DRG) and the spinal dorsal horn in rats, while total MSK-1 (t-MSK-1) did not change significantly. Intrathecal injection of the MSK-1 inhibitor SB747651A partially reversed established neuropathic pain. Additionally, intrathecal administration of MSK-1 siRNA either preoperatively or 7 days postoperatively relieves the development and maintenance of pain, respectively. Meanwhile, the expression levels of p-H3S10, a downstream target of MSK-1, also displayed a significant increase after SNL. And these changes could be reversed by using MSK-1 siRNA. Collectively, the increase of MSK-1 induced by SNL participates in the development and maintenance of neuropathic pain by regulating the expression of p-H3S10 in DRG and spinal dorsal horn. Concentrating on MSK-1 may result in a novel approach to the treatment of neuropathic pain.http://www.sciencedirect.com/science/article/pii/S0361923024002697Neuropathic painMSK-1DRGSpinal cordP-H3S10 |
| spellingShingle | Li Wang Yan Gao Yiming Qiao Xueli Wang Zongyi Liang Ji-Tian Xu Liren Li Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn Brain Research Bulletin Neuropathic pain MSK-1 DRG Spinal cord P-H3S10 |
| title | Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn |
| title_full | Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn |
| title_fullStr | Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn |
| title_full_unstemmed | Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn |
| title_short | Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn |
| title_sort | activation of msk 1 exacerbates neuropathic pain through histone h3 phosphorylation in the rats dorsal root ganglia and spinal dorsal horn |
| topic | Neuropathic pain MSK-1 DRG Spinal cord P-H3S10 |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024002697 |
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