Hydrogen-rich saline controls remifentanil-induced hypernociception and NMDA receptor NR1 subunit membrane trafficking through GSK-3β in the DRG in rats.
Linlin Zhang, Ruichen Shu, Chunyan Wang, Haiyun Wang, Nan Li, Guolin Wang · Brain research bulletin · 2014
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Independent study record
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H2HUBB TAKEAWAY
This preclinical study evaluated hydrogen-rich saline in rats. These results are preclinical and suggest molecular hydrogen's therapeutic potential in the condition studied. Further human research is needed to establish clinical effectiveness.
What the Researchers Studied
However, whether and how hydrogen-rich saline, as an effective anti-inflammatory drug, could prevent hyperalgesia through affecting peripheral sensitization caused by NMDAR activation remains to be explored.
How Molecular Hydrogen Was Used
To test these effects, hydrogen-rich saline (2.5, 5 or 10 ml/kg) was administrated intraperitoneally after remifentanil infusion, NMDAR antagonist MK-801 or GSK-3β inhibitor TDZD-8 was administrated intravenously before remifentanil infusion in rats. The researchers examined time course of hydrogen concentration in blood after hydrogen-rich saline administration.
What the Researchers Found
The researchers also discovered that hydrogen-rich saline not 2.5 ml/kg but 5 and 10 ml/kg could dose-dependently attenuate mechanical and thermal hyperalgesia without affecting baseline nociceptive threshold, reduce expressions of inflammatory mediators (TNF-α, IL-1β, and IL-6) and decrease NR1 trafficking mediated by GSK-3β, and minimal effective concentration was observed to be higher than 10 μmol/L, namely peak concentration in arterial blood after administration of HRS 2.5 ml/kg without any influence on hyperalgesia. The researchers also discovered that hydrogen-rich saline not 2.5 ml/kg but 5 and 10 ml/kg could dose-dependently attenuate mechanical and thermal hyperalgesia without affecting baseline nociceptive threshold, reduce expressions of inflammatory mediators (TNF-α, IL-1β, and IL-6) and decrease NR1 trafficking mediated by GSK-3β, and minimal effective concentration was observed to be higher than 10 μmol/L, namely peak concentration in arterial blood after administration of HRS 2.5 ml/kg without any influence on hyperalgesia.
H₂ Mechanisms / Biological Findings
However, whether and how hydrogen-rich saline, as an effective anti-inflammatory drug, could prevent hyperalgesia through affecting peripheral sensitization caused by NMDAR activation remains to be explored.
Authors’ Conclusion
The authors concluded that antihyperalgesic effect of hydrogen-rich saline might depend predominantly on its ability to reverse NR1 trafficking via inhibition of GSK-3β activity in DRG in a dose-dependent manner.