Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain
| Autor: | Zong‑Wang Zhang, Lei Liu, Xiu‑Juan Gao, Zhi‑Jian Fu, Chun‑Guang Ren, Xian‑Wen Liu, Ping Zhang, Ji‑Hua Hu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty CCR2 monocyte chemoattractant protein-1 C-C chemokine receptor type 2 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) Internal medicine morphine tolerance medicine Bone pain Bone cancer business.industry Monocyte spinal cord General Medicine Articles medicine.disease Spinal cord 030104 developmental biology medicine.anatomical_structure Endocrinology Neuropathic pain Immunology Morphine bone cancer pain medicine.symptom business Cancer pain 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-0981 |
| Popis: | Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain. |
| Databáze: | OpenAIRE |
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