# Spinal peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via enhancement of divalent metal transporter 1 without iron-responsive element-mediated iron accumulation in rats.
> ラットにおけるレミフェンタニル誘発術後痛覚過敏に対する脊髄ペルオキシナイトライトの関与：鉄応答配列非依存性DMT1を介した鉄蓄積機序の検討


## Abstract

This rat study examined the mechanism underlying postoperative hyperalgesia following remifentanil-based intraoperative analgesia. Thermal and mechanical hyperalgesia developed at 48 hours post-surgery. In spinal cord tissue, levels of 3-nitrotyrosine (1.22 ± 0.18 vs. 0.25 ± 0.05), nitrated manganese superoxide dismutase (1.01 ± 0.1 vs. 0.19 ± 0.03), and DMT1(-)IRE expression (1.42 ± 0.19 vs. 0.33 ± 0.06) were markedly elevated, along with iron concentration (12.87 ± 1.14 vs. 5.26 ± 0.61 μg/g), while DMT1(+)IRE remained unchanged. Administration of hydrogen-rich saline, which selectively decomposes peroxynitrite, reduced DMT1(-)IRE overexpression, attenuated iron accumulation, and alleviated hyperalgesia. An iron chelator also suppressed hyperalgesia in a dose-dependent fashion, supporting the role of iron in this nociceptive process.

### Mechanism

Spinal peroxynitrite upregulates DMT1(-)IRE, causing abnormal iron accumulation that promotes NMDA-mediated neurotoxicity and postoperative hyperalgesia. Hydrogen-rich saline selectively scavenges peroxynitrite, thereby suppressing DMT1(-)IRE overexpression and reducing iron-dependent nociceptive signaling.

## Bibliographic

- **Authors**: Shu RC, Zhang LL, Wang CY, Li N, Wang H, Xie K, et al.
- **Journal**: Anesthesiology
- **Year**: 2015
- **PMID**: [25501899](https://pubmed.ncbi.nlm.nih.gov/25501899/)
- **DOI**: [10.1097/ALN.0000000000000562](https://doi.org/10.1097/ALN.0000000000000562)
- **Study type**: animal study
- **Delivery route**: injection / infusion
- **Effect reported**: positive

## Delivery context

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).

## Safety notes

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 25501899. https://h2-papers.org/en/papers/25501899
> **Source**: PubMed PMID [25501899](https://pubmed.ncbi.nlm.nih.gov/25501899/)