The Effect of Perioperative Hydrogen Inhalation on Post-operative Pain and Inflammation Cytokines

Hydrogen is odorless, colorless gas existing in natural environment. It was traditionally thought as biologically inert gas, which means it does not participate in biological process. However, recent studies have demonstrated that ingestion of hydrogen have exerted therapeutic effect on skin squamous cell carcinoma and parasitic hepatitis. Ingestion of hydrogen could also attenuate ischemic-reperfusion injury after stroke by removing reactive oxygen species (ROS). Multiple studies also demonstrated that ingestion of hydrogen exhibit anti-inflammatory effect, leading to less post-operative cognitive impairment, lung graft injury in brain-dead mice and acute lung injury.

Means of hydrogen ingestion include oral, inhalation or intravenous injection. Inhalation through simple mask, nasal cannula or ventilator is most convenient way. It has been proved that low concentration of hydrogen inhalation (1%-4%) is effective and safe without causing adverse effects on hemodynamic, respiration or even data of arterial blood gas analysis. High concentration of hydrogen inhalation is proven to be harmless and is often used in diving, treating decompression sickness and preventing arterio-venous thromboembolism.

Current data suggests that microglial cells in dorsal root ganglion are activated by danger-associated molecular pattern (DAMP) through toll-like receptor response (TLR) after external insults. Lipopolysaccharides (LPS) are recognized as TLR-4 receptor agonist and data revealed that LPS is associated with significant neuroinflammation and chronic pain process. Peripheral blood monocyte cells(PBSC) could have pro- (e.g. Tumor necrosis factor-α(TNF-α)、Interleukin-6(IL-6)、Interferon-γ(INF-γ) ) and anti- inflammation (e.g. IL-4、IL-5、IL-9、IL-10) cytokines release after LPS stimulation.

Current data suggests that hydrogen-rich water ingestion could reduce inflammation and pain score in animal model. Hydrogen inhalation is associated with decrease of pro-inflammation cytokines, such as IL-1β, IL-6, TNF-α and INF-γ. Besides, hydrogen inhalation could lead to reduction of pain in rats with high level spinal cord injury.

In addition to observing the difference of pain score between groups, we could also observe the differences between pro- and anti- inflammation cytokines in PBSC after LPS stimulation in patients receiving or not receiving hydrogen inhalation. This could tell us whether the inflammation process is inhibited in cellular level by hydrogen inhalation. To our knowledge, there is no human clinical trials discussing the effect of hydrogen inhalation on chronic pain. We hope to understand the actual impact of hydrogen inhalation on post-operative pain score and inflammation. Further larger scale randomized clinical trials could be carried on based on this result.