科研之友
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摘要
Neuroinflammatory response in spinal dorsal horn has been demonstrated to be a critical factor in oxaliplatin-induced pain. Melatonin has been shown to have anti-inflammatory and anti-allodynia effects in both preclinical and clinical studies. In the present study, we investigated the role of systemic administration of melatonin on oxaliplatin-induced pain. Intraperitoneal (i.p.) injection with oxaliplatin induced significantly mechanical allodynia and thermal hyperalgesia. Melatonin (i.p.) significantly alleviated mechanical allodynia and thermal hyperalgesia in the oxaliplatin but not sham-treated rats. The attenuation of nociceptive response persisted at least to 3 days after melatonin injection, throughout the entire observing Immunohistochemistry showed that oxaliplatin induced a significant increase of glial fibrillary acidic protein (GFAP) immunodensities, which could be suppressed by melatonin. Western blotting showed that GFAP protein levels were significantly elevated in the oxaliplatin-vehicle group. Melatonin significantly decreased oxaliplatin-induced upregulation of GFAP expressions. Oxaliplatin injection also enhanced the messenger RNA (mRNA) expressions of cytokines including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and chemokines including monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1 (MIP-1 alpha) in the spinal dorsal horn, which could be significantly repressed by melatonin. In vitro study showed that mRNA levels of TNF-alpha, IL-1 beta, MCP-1, and MIP-1 alpha in primarily astrocytes were significantly increased after lipopolysaccharide (LPS, 1 mu g/ml) stimulation. Melatonin (10 and 100 mu M) greatly inhibited synthesis of these inflammatory mediators, in a dose-related manner. Conclusively, our data provide a novel implication of anti-nociceptive mechanism of melatonin in chemotherapy-related pain.
- 出版日期2017-12
- 单位浙江大学
