SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway
Background. Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Methods...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Pain Research and Management |
| Online Access: | http://dx.doi.org/10.1155/2020/4245968 |
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| author | Yangyang Li Lei Wang Guotao Zhang Xueli Qiao Mingxing Zhang |
| author_facet | Yangyang Li Lei Wang Guotao Zhang Xueli Qiao Mingxing Zhang |
| author_sort | Yangyang Li |
| collection | DOAJ |
| description | Background. Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Methods. In this context, the effect of SIRT1 on neuropathic pain in the VTA-NAc pathway was investigated in the model of chronic constrictive injury (CCI). Results. SIRT1 was localized in the VTA neurons in naive mice. The expression of SIRT1 was decreased in the contralateral VTA of CCI mice. After microinjection of SRT1720 (an activator of SIRT1) in the contralateral VTA of CCI mice, the established thermal hyperalgesia was attenuated. However, it was further exacerbated by EX-527 (an inhibitor of SIRT1). The elevated level of acetyl-histone 3 was reduced by SRT1720 but further elevated by EX-527 in the contralateral VTA of CCI mice. The increased expression of Fos in both VTA and NAc was downregulated by SRT1720 but further upregulated by EX-527 in CCI mice. Conclusions. The discovery of the effect of SIRT1 on neuropathic pain in the VTA represents an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway. |
| format | Article |
| id | doaj-art-e8c51e2c4ea74cc6a1f02bada27baea8 |
| institution | DOAJ |
| issn | 1203-6765 1918-1523 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pain Research and Management |
| spelling | doaj-art-e8c51e2c4ea74cc6a1f02bada27baea82025-08-20T03:21:10ZengWileyPain Research and Management1203-67651918-15232020-01-01202010.1155/2020/42459684245968SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc PathwayYangyang Li0Lei Wang1Guotao Zhang2Xueli Qiao3Mingxing Zhang4Department of Anesthesiology, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223001, ChinaDepartment of Anesthesiology, The Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an 223001, ChinaDepartment of Pharmacy, The Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an 223001, ChinaDepartment of Pharmacy, The Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an 223001, ChinaDepartment of Pharmacy, The Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an 223001, ChinaBackground. Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Methods. In this context, the effect of SIRT1 on neuropathic pain in the VTA-NAc pathway was investigated in the model of chronic constrictive injury (CCI). Results. SIRT1 was localized in the VTA neurons in naive mice. The expression of SIRT1 was decreased in the contralateral VTA of CCI mice. After microinjection of SRT1720 (an activator of SIRT1) in the contralateral VTA of CCI mice, the established thermal hyperalgesia was attenuated. However, it was further exacerbated by EX-527 (an inhibitor of SIRT1). The elevated level of acetyl-histone 3 was reduced by SRT1720 but further elevated by EX-527 in the contralateral VTA of CCI mice. The increased expression of Fos in both VTA and NAc was downregulated by SRT1720 but further upregulated by EX-527 in CCI mice. Conclusions. The discovery of the effect of SIRT1 on neuropathic pain in the VTA represents an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway.http://dx.doi.org/10.1155/2020/4245968 |
| spellingShingle | Yangyang Li Lei Wang Guotao Zhang Xueli Qiao Mingxing Zhang SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway Pain Research and Management |
| title | SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway |
| title_full | SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway |
| title_fullStr | SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway |
| title_full_unstemmed | SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway |
| title_short | SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway |
| title_sort | sirt1 mediates neuropathic pain induced by sciatic nerve chronic constrictive injury in the vta nac pathway |
| url | http://dx.doi.org/10.1155/2020/4245968 |
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