Hydrogen Therapy Blocks Opioid-Induced Pain Hypersensitivity in Rats
- Authors
- Linlin Zhang, Ruichen Shu, Chunyan Wang, Haiyun Wang, Nan Li, Guo-Lin Wang
- Journal
- Brain Research Bulletin
- Year
- 2014
- DOI
- 10.1016/j.brainresbull.2014.05.005
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Opioid-Induced Hyperalgesia
- Body System
- Nervous System
TL;DR
Hydrogen-rich saline can reduce pain sensitivity and inflammation in rats by interfering with a specific pain-related pathway in nerve cells.
Key Finding
Hydrogen-rich saline reduced opioid-induced pain hypersensitivity in rats by inhibiting a protein called GSK-3β and preventing NMDA receptor trafficking in nerve cells, with doses of 5 and 10 ml/kg showing dose-dependent effects.
Summary
This rat study investigated whether hydrogen-rich saline could reduce pain hypersensitivity caused by remifentanil, a strong opioid painkiller. Researchers found that when rats received hydrogen-rich saline after remifentanil infusion, it reduced pain sensitivity in a dose-dependent manner (higher doses worked better) by decreasing inflammation and blocking certain pain-signaling pathways in nerve tissue.
Practical Takeaway
This is early-stage animal research showing hydrogen-rich saline may help prevent pain hypersensitivity from opioid use through anti-inflammatory mechanisms. However, these findings are from rats only and have not been tested in humans, so it is too early to draw conclusions about potential benefits for people taking opioid medications.
Abstract
Background: Although NMDAR trafficking mediated by GSK-3β involvement in transmission of pronociceptive messages in the spinal cord has been confirmed by our previous studies, whether NMDAR trafficking is implicated in peripheral sensitization remains equivocal. It is demonstrated that inflammation is associated with spinal NMDAR-containing nociceptive neurons activation and the maintenance of opioid induced pain hypersensitivity. 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. Methods: 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. We examined time course of hydrogen concentration in blood after hydrogen-rich saline administration. Mechanical and thermal hyperalgesia were evaluated by measuring PWT and PWL for 48 post-infusion hours, respectively. Western blotting and real-time qPCR assay were applied to analyze the NR1 membrane trafficking, GSK-3β expression and activity in DRG. Inflammatory mediators (TNF-α, IL-1β, and IL-6) expressions in DRG were also analyzed. Results: We found that NR1 membrane trafficking in DRG increased, possibly due to GSK-3β activation after remifentanil infusion. We 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. Conclusion: Our results indicated 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.