Gas therapy: an innovative application for intervertebral disc degeneration

FactsGas therapy represents a novel and promising therapeutic paradigm for intervertebral disc degeneration, utilizing bioactive gases to modulate oxidative stress, inflammation, and extracellular matrix metabolism.Certain gas therapies, such as medical ozone and hyperbaric oxygen, have already been translated into clinical use for intervertebral disc degeneration, demonstrating efficacy in pain alleviation, disinfection, and improving functional outcomes through minimally invasive delivery.The core mechanisms of gas therapeutics involve the restoration of disc microenvironment homeostasis via specific actions, including reactive oxygen species scavenging, suppression of inflammatory cytokines, inhibition of inflammasome activity, and enhancement of collagen synthesis.Combination strategies integrating gas therapy with other regenerative approaches-such as stem cell transplantation, bioactive scaffolds, or drug delivery systems-exhibit synergistic potential for amplifying anti-inflammatory, antioxidant, and anabolic effects in disc repair.Open questionsWhat are the precise molecular mechanisms and signaling pathways (e.g., hydrogen-mediated nuclear factor erythroid 2-related factor 2 activation, hydrogen sulfide-dependent extracellular matrix regulation) through which gaseous mediators exert their therapeutic effects in human disc cells under pathological microenvironments?How can physiologically relevant disease models-such as human disc organoids or large animal models under biomechanical loading-be developed and utilized to better recapitulate human intervertebral disc degeneration pathophysiology and improve the translational validity of preclinical gas therapy research?What is the clinical efficacy and safety of gas therapeutic protocols in large-scale, multicenter randomized controlled trials? How can standardized treatment parameters and personalized regimens be established for different subtypes and etiologies of intervertebral disc degeneration? Environmental gaseous molecules extensively participate in human physiological and pathological regulation through differential biological effects. Gas transmitter-based therapeutic strategies, as emerging intervention modalities, have demonstrated significant translational value in intervertebral disc degeneration management. The intervertebral disc degeneration susceptibility to progressive degenerative pathology stems from its unique avascular nature and complex biomechanical microenvironment, while conventional therapies face limitations in efficacy and carry invasive risks. This review systematically delineates innovative applications of gaseous therapeutics for intervertebral disc degeneration, encompassing clinically established ozone and hyperbaric oxygen therapies alongside preclinical-stage hydrogen, hydrogen sulfide, and nitric oxide interventions. Comprehensive analyses address molecular properties, biological functions, and mechanistic actions. Current evidence indicates that gas therapies significantly alleviate pain and improve functional impairment through targeted modulation of oxidative stress-inflammation-apoptosis cascades and extracellular matrix metabolic dysregulation. Their minimally invasive precision delivery capabilities and multimodal bio-regulatory advantages offer groundbreaking diagnostic and therapeutic strategies for intervertebral disc degeneration, exhibiting well-defined clinical translation potential.