Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis
Neuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and diff...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/6420425 |
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| author | Yajun Deng Liang Yang Qiqi Xie Fengbiao Yang Guoqiang Li Guangzhi Zhang Shaoping Li Zuolong Wu Jing Wang Xuewen Kang |
| author_facet | Yajun Deng Liang Yang Qiqi Xie Fengbiao Yang Guoqiang Li Guangzhi Zhang Shaoping Li Zuolong Wu Jing Wang Xuewen Kang |
| author_sort | Yajun Deng |
| collection | DOAJ |
| description | Neuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and differentially expressed genes were screened using the R software. cytoHubba was used to screen for hub genes. A spared nerve injury (SNI) rat model was established, and the paw withdrawal threshold was determined using von Frey filaments. Western blotting and immunofluorescence were used to detect the expression and cellular localization, respectively, of key proteins in the spinal cord. Western blot, ELISA, and TUNEL assays were used to detect cell signal transduction, inflammation, and apoptosis, respectively. Pka was identified as a key gene involved in neuropathic pain. After SNI, mechanical allodynia occurred, PKA expression in the spinal cord increased, the p38MAPK pathway was activated, and spinal cord inflammation and apoptosis occurred in rats. PKA colocalized with neurons, astrocytes, and microglia, and apoptotic cells were mainly neurons. Intrathecal injection of a PKA inhibitor not only relieved mechanical hyperalgesia, inflammatory reaction, and apoptosis in SNI rats but also inhibited p38MAPK pathway activation. However, intrathecal injection of a p38MAPK inhibitor attenuated mechanical hyperalgesia, inflammation, and apoptosis, but did not affect PKA expression. In conclusion, PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis. |
| format | Article |
| id | doaj-art-1e562c5f1e54486295690d76c14afcd2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1e562c5f1e54486295690d76c14afcd22025-02-03T06:04:38ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/64204256420425Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell ApoptosisYajun Deng0Liang Yang1Qiqi Xie2Fengbiao Yang3Guoqiang Li4Guangzhi Zhang5Shaoping Li6Zuolong Wu7Jing Wang8Xuewen Kang9Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaThe Department of Osteoporosis, The People’s Hospital of Baoan District, Shenzhen, Guangdong Province 518000, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, ChinaNeuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and differentially expressed genes were screened using the R software. cytoHubba was used to screen for hub genes. A spared nerve injury (SNI) rat model was established, and the paw withdrawal threshold was determined using von Frey filaments. Western blotting and immunofluorescence were used to detect the expression and cellular localization, respectively, of key proteins in the spinal cord. Western blot, ELISA, and TUNEL assays were used to detect cell signal transduction, inflammation, and apoptosis, respectively. Pka was identified as a key gene involved in neuropathic pain. After SNI, mechanical allodynia occurred, PKA expression in the spinal cord increased, the p38MAPK pathway was activated, and spinal cord inflammation and apoptosis occurred in rats. PKA colocalized with neurons, astrocytes, and microglia, and apoptotic cells were mainly neurons. Intrathecal injection of a PKA inhibitor not only relieved mechanical hyperalgesia, inflammatory reaction, and apoptosis in SNI rats but also inhibited p38MAPK pathway activation. However, intrathecal injection of a p38MAPK inhibitor attenuated mechanical hyperalgesia, inflammation, and apoptosis, but did not affect PKA expression. In conclusion, PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis.http://dx.doi.org/10.1155/2020/6420425 |
| spellingShingle | Yajun Deng Liang Yang Qiqi Xie Fengbiao Yang Guoqiang Li Guangzhi Zhang Shaoping Li Zuolong Wu Jing Wang Xuewen Kang Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis Mediators of Inflammation |
| title | Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis |
| title_full | Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis |
| title_fullStr | Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis |
| title_full_unstemmed | Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis |
| title_short | Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis |
| title_sort | protein kinase a is involved in neuropathic pain by activating the p38mapk pathway to mediate spinal cord cell apoptosis |
| url | http://dx.doi.org/10.1155/2020/6420425 |
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