Hydrogen Therapy Prevents Morphine Tolerance in Pain Management Study
- Authors
- Qing Li, Haifang Zhang, Zhen Jia, Linlin Zhang, Yize Li, Rubin Xu, Chunyan Wang, Yonghao Yu
- Journal
- Neuroscience Letters
- Year
- 2021
- DOI
- 10.1016/j.neulet.2021.135847
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Morphine Tolerance
- Body System
- Nervous System
TL;DR
Pretreating rats with hydrogen-rich saline reduced their tolerance to morphine by decreasing inflammation and changes in the brain's communication system.
Key Finding
Hydrogen-enriched saline prevented morphine tolerance in rats by reducing inflammation and blocking harmful changes in pain-processing proteins in the spinal cord.
Summary
Researchers gave rats morphine to create tolerance (a condition where the drug becomes less effective over time), then treated some rats with hydrogen-enriched saline before each morphine dose. Hydrogen-enriched saline reduced morphine tolerance and decreased inflammation and damage in the spinal cord that normally occurs with repeated morphine use. The effect was stronger at higher doses of hydrogen-enriched saline.
Practical Takeaway
This rat study suggests hydrogen may help prevent morphine tolerance by reducing spinal cord inflammation, but it is early-stage animal research only. Human studies would be needed to determine if this approach could help people taking opioid pain medications long-term.
Abstract
The development and maintenance of morphine tolerance showed association with neuroinflammation and dysfunction of central glutamatergic system (such as nitration of glutamate transporter). Recent evidence indicated that hydrogen could reduce the levels of neuroinflammation and oxidative stress, but its role in morphine tolerance has not been studied. The rats were intrathecally administered with morphine (10 µg/10 µl each time, twice/day for 5 days). Hydrogen enriched saline (HS) or saline was given intraperitoneally at 1, 3 and 10 ml/kg for 10 min before each dose of morphine administration. The tail-flick latency, mechanical threshold and thermal latency were assessed one day (baseline) before and daily for up to 5 days during morphine injection. The pro-inflammatory cytokine expressions [tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6)] (by western blotting), astrocyte activation (by immunofluorescence and western blotting), and nitration of glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) (by immunoprecipitation), membrane and total expression of N-methyl-D-aspartic acid (NMDA) receptor NR1 and NR2B subunits were carried out in the spinal dorsal horns. Chronic morphine administration induced antinociceptive tolerance, and together led to increased TNF-α, IL-1β and IL-6 expression, astrocyte activation, GLT-1 and GS nitration, increased membrane and total NR1, NR2B expression. Injection of HS attenuated morphine tolerance in a dose-dependent manner, decreased proinflammatory cytokine expression, inhibited astrocyte activation, decreased GLT-1 and GS nitration, and inhibited membrane trafficking of NMDA receptor. Our result showed that hydrogen pretreatment prevented morphine tolerance by reducing neuroinflammation, GLT-1, GS nitration, NMDA receptor trafficking in the spinal dorsal horn. Pretreatment with hydrogen might be considered as a novel therapeutic strategy for the prevention of morphine tolerance.