ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Pain Mechanisms and Modulators
Nrf2/HO-1-sulfiredoxin1 pathway involved in nanobubble hydrogen-dissolved water-mediated protective effects by ultrasound-guided early local injection in a rat model of chronic constriction injury-induced neuropathic pain
Provisionally accepted- 1The Affiliated Hospital of Qingdao University, Qingdao, China
- 2The Third People's Hospital of Qingdao, Qingdao, China
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Neuropathic pain (NP) is a common and intractable form of chronic pain. Hydrogen (H2)-rich water has been shown to protect against NP after oral consumption or intrathecal or intraperitoneal injection. Therefore, this study aimed to observe the effects of ultrasound-guided local injection with nanobubble H2-dissolved water (NHW) in a chronic constriction injury (CCI) model of the rat sciatic nerve and to elucidate the underlying mechanism. The CCI rats received NHW at low or high concentrations 1 or 3 times (n = 6). Compared with the low concentration, in the high concentration group, the paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL) were attenuated on days 1, 3, 5, 7, and 14 after CCI (P < 0.05). On day 14, nerve injury, the inflammatory response, and oxidative stress injury were significantly more relieved at high concentrations than at low concentrations, and the effect was greater at multiple doses (3 times) at high concentrations (P < 0.05), as were the increases in the protein and mRNA levels of Nrf2/HO-1 and sulfiredoxin-1. In conclusion, ultrasound-guided early local injection of NHW attenuated sciatic nerve injury alleviated mechanical allodynia and thermal hyperalgesia and inhibited inflammation and oxidative stress damage via the Nrf2/HO-1-sulfiredoxin1 pathway in a rat model of CCI.
Keywords: Nanobubble hydrogen-dissolved water, chronic constriction injury, neuropathic pain, Ultrasound-guided, Nrf2/HO-1, Sulfiredoxin1
Received: 22 Jul 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Yu, Yin, Ma, Zhang and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chao Meng, mengchao@qdu.edu.cn
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