General Research
Model: rat
Spinal peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via enhancement of divalent metal transporter 1 without iron-responsive element-mediated iron accumulation in rats
Simplified Version Available
The Hidden Cause of Postoperative Pain: How a Common Anesthetic Affects the Spine
Researchers in China found that the anesthetic remifentanil increases production of a damaging molecule in the spine, leading to greater pain sensitivity after surgery. This discovery could lead to better pain management strategies. Understanding how medications affect the spine and pain perception is crucial for improving patient recovery.
Read Simplified ArticleAbstract
Publish Year 2015 Country China Rank Positive Journal Anesthesiology Primary Topic Spine Secondary TopicSurgery/Transplantation Model Rat Tertiary TopicDrug Toxicity (Remifantanil) Vehicle Saline (Dissolved) pH Neutral Application Injection Comparison Complement
Background
Methods: Behavior testing was performed in rat model at different time points. Three-nitrotyrosine, nitrated manganese superoxide dismutase, and DMT1 with/without iron-responsive element [DMT1(+)IRE and DMT1(-)IRE] in spinal cord were detected by Western blot and immunohistochemistry. Spinal iron concentration was measured using the Perl stain and atomic absorption spectrophotometer. Hydrogen-rich saline imparting selectivity for peroxynitrite decomposition and iron chelator was applied in mechanistic study on the roles of peroxynitrite and iron, as well as the prevention of hyperalgesia.
Methods
Results: Remifentanil induced thermal and mechanical hyperalgesia at postoperative 48 h. Compared with control, there were higher levels of 3-nitrotyrosine (mean ± SD, hyperalgesia vs. control, 1.22 ± 0.18 vs. 0.25 ± 0.05, n = 4), nitrated manganese superoxide dismutase (1.01 ± 0.1 vs. 0.19 ± 0.03, n = 4), DMT1(-)IRE (1.42 ± 0.19 vs. 0.33 ± 0.06, n = 4), and iron concentration (12.87 ± 1.14 vs. 5.26 ± 0.61 μg/g, n = 6) in remifentanil-induced postoperative hyperalgesia, while DMT1(+)IRE was unaffected. Eliminating peroxynitrite with hydrogen-rich saline protected against hyperalgesia and attenuated DMT1(-)IRE overexpression and iron accumulation. Iron chelator prevented hyperalgesia in a dose-dependent manner. Conclusions: Our study identifies that spinal peroxynitrite activates DMT1(-)IRE, leading to abnormal iron accumulation in remifentanil-induced postoperative hyperalgesia, while providing the rationale for the development of molecular hydrogen and 'iron-targeted' therapies.