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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Liu, Dandan Zhang, Mingyue Xu, Xiaohai Zhong, Xuelai Ma, Chao Zheng, Xiaoyu Wu, Xiaohong Wang, Guonian |
| Abstract | While low-dose cannabinoid 2 (CB2) receptor agonists attenuate morphine tolerance in cancer pain models, chemokine ligand 12 (CXCL12)/chemokine receptor 4 (CXCR4) expression induces morphine tolerance. Whether CB2 receptor agonists attenuate morphine tolerance by modulating CXCL12/CXCR4 signaling or whether CXCL12/CXCR4 signaling affects the mu opioid receptor (MOR) in the development of morphine tolerance in cancer pain remains unclear. In this study, we investigated the attenuation of morphine tolerance by a non-analgesic dose of the CB2 receptor agonist AM1241, focusing specifically on the modulation of CXCL12/CXCR4 signaling and its effect on the MOR. Rats received intrathecal Walker 256 tumor cell implantations and were treated with morphine combined with the intrathecal injection of AM1241 or the CB2 receptor antagonists AM630 and AM1241, or a CXCL12-neutralizing antibody, exogenous CXCL12, or the CXCR4 antagonist AMD3100. Our results show that CXCL12 and CXCR4 levels increased significantly in morphine-tolerant rats and were reduced by AM1241 pretreatment, which was reversed by AM630. CXCL12/CXCR4 expression accelerated the development of morphine tolerance and downregulated MOR expression. CXCR4 colocalized with MOR and CB2. Therefore, a non-analgesic dose of AM1241 attenuated morphine tolerance via CXCL12/CXCR4 signaling, whereas CXCL12/CXCR4 signaling participated in the development of morphine tolerance, potentially by modulating MOR expression in Walker 256 tumor-bearing rats. Graphical Abstract |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-02207-6.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-02207-6 |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-12-18 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Mu opioid receptor Cancer pain Cannabinoid 2 Chemokine ligand 12/chemokine receptor 4 Morphine tolerance Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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