Hydrogen Therapy Prevents Post-Surgery Pain from Opioid Use in Rats

Authors
Journal
Anesthesiology
Year
DOI
10.1097/ALN.0000000000000562
Study Type
Rat
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Post-operative Hyperalgesia
Body System
Nervous System

TL;DR

This study suggests that a compound called peroxynitrite may cause increased pain sensitivity after surgery by causing iron to build up in the spinal cord, and treatments that remove peroxynitrite or iron could prevent this pain.

Key Finding

Hydrogen-rich saline prevented remifentanil-induced pain sensitivity in rats by selectively breaking down peroxynitrite and reducing abnormal iron accumulation in the spinal cord.

Summary

This rat study investigated why remifentanil, a powerful painkiller used during surgery, can cause increased pain sensitivity after the operation. Researchers found that remifentanil triggers a harmful chemical called peroxynitrite in the spinal cord, which causes iron to accumulate abnormally. When they treated rats with hydrogen-rich saline (a salt solution containing dissolved hydrogen gas), it reduced peroxynitrite levels, prevented iron buildup, and protected against post-surgery pain sensitivity.

Practical Takeaway

This is an early-stage animal study suggesting hydrogen may help prevent opioid-related pain complications, but it has not been tested in humans. The findings are preliminary and would need to be validated in clinical trials before any conclusions could be drawn about hydrogen water's usefulness for this purpose in people.

Abstract

AbstractAbstract Spinal cord levels of 3-nitrotyrosine, a biomarker for peroxynitrite production, were elevated after remifentanil infusion in rats. The administration of hydrogen-rich saline both reduced peroxynitrite production and reduced hyperalgesia after remifentanil infusion. Background: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation. Iron accumulation mediated by divalent metal transporter 1 (DMT1) plays a key role in N-methyl-d-aspartate neurotoxicity. This study aims to determine whether peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via DMT1-mediated iron accumulation. 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. 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.