Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells
Mesenchymal stem cells have cannabinoid (CB) receptors type 1 and type 2 and can alleviate a variety of neuropathic pains, including chronic constriction injury (CCI). A selective CB2 receptor agonist is AM1241. In the present study, it was found that mice with CCI displayed a longer duration of mec...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/7025473 |
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| author | Junran Xie Jinxuan Ren Na Liu Chengwei Wu Dongju Xiao Huanyu Luo Jingxian Du |
| author_facet | Junran Xie Jinxuan Ren Na Liu Chengwei Wu Dongju Xiao Huanyu Luo Jingxian Du |
| author_sort | Junran Xie |
| collection | DOAJ |
| description | Mesenchymal stem cells have cannabinoid (CB) receptors type 1 and type 2 and can alleviate a variety of neuropathic pains, including chronic constriction injury (CCI). A selective CB2 receptor agonist is AM1241. In the present study, it was found that mice with CCI displayed a longer duration of mechanical and thermal analgesia when intrathecally (i.t.) injected with AM1241-treated mesenchymal stem cells, compared to those injected with untreated mesenchymal stem cells or AM1241 alone. Moreover, CCI-induced upregulation of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (p-ERK1/2) was inhibited following i.t. injection of AM1241-treated mesenchymal stem cells and this inhibition was noticeably higher compared to injection with untreated mesenchymal stem cells. The expression of transforming growth factor-β1 (TGF-β1) was also analyzed in the dorsal root ganglion (DRGs) and spinal cord of CCI mice. In untreated CCI mice, expression of TGF-β1 was increased, whereas pretreatment with AM1241-treated mesenchymal stem cells regulated the expression of TGF-β1 on 10 days and 19 days after surgery. In addition, i.t. injection of exogenous TGF-β1 slightly alleviated neuropathic pain whilst neutralization of TGF-β1 potently blocked the effect of AM1241-treated mesenchymal stem cells on thermal hyperalgesia and mechanical allodynia of CCI mice. In an in vitro experiment, AM1241 could enhance the release of TGF-β1 in the supernatant of BMSCs after lipopolysaccharide (LPS) simulation. Taken together, the findings of the current study show that i.t. administration of AM1241-treated mesenchymal stem cells has a positive effect on analgesia and that TGF-β1 and p-ERK1/2 may be the molecular signaling pathway involved in this process. |
| format | Article |
| id | doaj-art-f544f778488f4f64a374ddb7f1df5683 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-f544f778488f4f64a374ddb7f1df56832025-02-03T01:12:01ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/70254737025473Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem CellsJunran Xie0Jinxuan Ren1Na Liu2Chengwei Wu3Dongju Xiao4Huanyu Luo5Jingxian Du6Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, ChinaDepartment of Anesthesiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, ChinaDepartment of Anesthesiology, Li Shui Hospital of Zhejiang University, Lishui 323000, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, ChinaJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, ChinaMesenchymal stem cells have cannabinoid (CB) receptors type 1 and type 2 and can alleviate a variety of neuropathic pains, including chronic constriction injury (CCI). A selective CB2 receptor agonist is AM1241. In the present study, it was found that mice with CCI displayed a longer duration of mechanical and thermal analgesia when intrathecally (i.t.) injected with AM1241-treated mesenchymal stem cells, compared to those injected with untreated mesenchymal stem cells or AM1241 alone. Moreover, CCI-induced upregulation of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (p-ERK1/2) was inhibited following i.t. injection of AM1241-treated mesenchymal stem cells and this inhibition was noticeably higher compared to injection with untreated mesenchymal stem cells. The expression of transforming growth factor-β1 (TGF-β1) was also analyzed in the dorsal root ganglion (DRGs) and spinal cord of CCI mice. In untreated CCI mice, expression of TGF-β1 was increased, whereas pretreatment with AM1241-treated mesenchymal stem cells regulated the expression of TGF-β1 on 10 days and 19 days after surgery. In addition, i.t. injection of exogenous TGF-β1 slightly alleviated neuropathic pain whilst neutralization of TGF-β1 potently blocked the effect of AM1241-treated mesenchymal stem cells on thermal hyperalgesia and mechanical allodynia of CCI mice. In an in vitro experiment, AM1241 could enhance the release of TGF-β1 in the supernatant of BMSCs after lipopolysaccharide (LPS) simulation. Taken together, the findings of the current study show that i.t. administration of AM1241-treated mesenchymal stem cells has a positive effect on analgesia and that TGF-β1 and p-ERK1/2 may be the molecular signaling pathway involved in this process.http://dx.doi.org/10.1155/2019/7025473 |
| spellingShingle | Junran Xie Jinxuan Ren Na Liu Chengwei Wu Dongju Xiao Huanyu Luo Jingxian Du Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells Stem Cells International |
| title | Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells |
| title_full | Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells |
| title_fullStr | Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells |
| title_full_unstemmed | Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells |
| title_short | Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells |
| title_sort | pretreatment with am1241 enhances the analgesic effect of intrathecally administrated mesenchymal stem cells |
| url | http://dx.doi.org/10.1155/2019/7025473 |
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