JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation
Background: Pain and depression are common complications in patients with advanced cancer, which significantly affects their quality of life and survival. Dysregulation of the JAK/STAT3 pathway in the central nervous system is associated with pain and brain inflammatory disorders, but its role in bo...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025000309 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206962010193920 |
|---|---|
| author | Shuyan Wu Jundan Jiang Danfeng Wang Daoyi Lin Mingxue Lin Pinzhong Chen Jianghu Chen Honghong Zhang Ying Wang Xiaohui Chen Xiaochun Zheng |
| author_facet | Shuyan Wu Jundan Jiang Danfeng Wang Daoyi Lin Mingxue Lin Pinzhong Chen Jianghu Chen Honghong Zhang Ying Wang Xiaohui Chen Xiaochun Zheng |
| author_sort | Shuyan Wu |
| collection | DOAJ |
| description | Background: Pain and depression are common complications in patients with advanced cancer, which significantly affects their quality of life and survival. Dysregulation of the JAK/STAT3 pathway in the central nervous system is associated with pain and brain inflammatory disorders, but its role in bone cancer pain (BCP) remains unclear. This study aimed to investigate the specific role of the JAK/STAT3 pathway in the amygdala in BCP. Methods: A BCP rat model was established by intratibial injection of MRMT-1 carcinoma cells. Pain behavior was assessed using the mechanical withdrawal threshold, while depression-like behavior was assessed using the sucrose preference and forced swim test. Changes in inflammatory factors and related protein expression levels in the amygdala were detected using western blotting, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of intra-amygdala injections of a lentivirus targeting retinoic acid-related orphan receptor γt (RORγt) (LV-shRORγt), nifuroxazide (a STAT3 antagonist), and colivelin (a STAT3 agonist) were evaluated. Results: Rats with BCP demonstrated increased microglial activation in the amygdala. Rats experiencing RORγt knockout in the amygdala showed reduced microglial activation levels. Nifuroxazide reduced Th17 cell differentiation, potentially alleviating pain and depression-like behaviors. To further explore the underlying relationship between the JAK/STAT3 pathway and Th17 cells, LV-shRORγt and a STAT3 agonist were co-administered. The inhibitory effect of LV-shRORγt counteracted the STAT3 agonist’s active effects. Conclusions: Our study showed that targeting JAK/STAT3 signaling alleviated pain- and depression-like behaviors in rats with BCP by inhibiting Th17 cell differentiation. |
| format | Article |
| id | doaj-art-90145f293fa44449817bb44973fc5060 |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-90145f293fa44449817bb44973fc50602025-02-07T04:46:46ZengElsevierBrain Research Bulletin1873-27472025-02-01221111218JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiationShuyan Wu0Jundan Jiang1Danfeng Wang2Daoyi Lin3Mingxue Lin4Pinzhong Chen5Jianghu Chen6Honghong Zhang7Ying Wang8Xiaohui Chen9Xiaochun Zheng10Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesia, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100029, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, ChinaDepartment of Anesthesiology, Fujian Medical University Teaching Hospital, Fujian Provincial Geriatric Hospital, Fuzhou 350003, ChinaDepartment of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, China; Corresponding author.Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, China; Fujian Emergency Medical Center, Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou 350000, China; Corresponding author at: Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, China.Background: Pain and depression are common complications in patients with advanced cancer, which significantly affects their quality of life and survival. Dysregulation of the JAK/STAT3 pathway in the central nervous system is associated with pain and brain inflammatory disorders, but its role in bone cancer pain (BCP) remains unclear. This study aimed to investigate the specific role of the JAK/STAT3 pathway in the amygdala in BCP. Methods: A BCP rat model was established by intratibial injection of MRMT-1 carcinoma cells. Pain behavior was assessed using the mechanical withdrawal threshold, while depression-like behavior was assessed using the sucrose preference and forced swim test. Changes in inflammatory factors and related protein expression levels in the amygdala were detected using western blotting, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of intra-amygdala injections of a lentivirus targeting retinoic acid-related orphan receptor γt (RORγt) (LV-shRORγt), nifuroxazide (a STAT3 antagonist), and colivelin (a STAT3 agonist) were evaluated. Results: Rats with BCP demonstrated increased microglial activation in the amygdala. Rats experiencing RORγt knockout in the amygdala showed reduced microglial activation levels. Nifuroxazide reduced Th17 cell differentiation, potentially alleviating pain and depression-like behaviors. To further explore the underlying relationship between the JAK/STAT3 pathway and Th17 cells, LV-shRORγt and a STAT3 agonist were co-administered. The inhibitory effect of LV-shRORγt counteracted the STAT3 agonist’s active effects. Conclusions: Our study showed that targeting JAK/STAT3 signaling alleviated pain- and depression-like behaviors in rats with BCP by inhibiting Th17 cell differentiation.http://www.sciencedirect.com/science/article/pii/S0361923025000309Bone cancer painDepressionJAK/STAT3 signalingTh17 differentiationNeuroinflammation |
| spellingShingle | Shuyan Wu Jundan Jiang Danfeng Wang Daoyi Lin Mingxue Lin Pinzhong Chen Jianghu Chen Honghong Zhang Ying Wang Xiaohui Chen Xiaochun Zheng JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation Brain Research Bulletin Bone cancer pain Depression JAK/STAT3 signaling Th17 differentiation Neuroinflammation |
| title | JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation |
| title_full | JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation |
| title_fullStr | JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation |
| title_full_unstemmed | JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation |
| title_short | JAK/STAT3 signaling promotes pain and depression-like behaviors in rats with bone cancer pain by regulating Th17 cell differentiation |
| title_sort | jak stat3 signaling promotes pain and depression like behaviors in rats with bone cancer pain by regulating th17 cell differentiation |
| topic | Bone cancer pain Depression JAK/STAT3 signaling Th17 differentiation Neuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025000309 |
| work_keys_str_mv | AT shuyanwu jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT jundanjiang jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT danfengwang jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT daoyilin jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT mingxuelin jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT pinzhongchen jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT jianghuchen jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT honghongzhang jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT yingwang jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT xiaohuichen jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation AT xiaochunzheng jakstat3signalingpromotespainanddepressionlikebehaviorsinratswithbonecancerpainbyregulatingth17celldifferentiation |