Gas therapy: an innovative application for intervertebral disc degeneration

Cai, Lu1; Ru, Bin2; Ren, Haijiang3; Cai, Fang2; Zeng, Lingyuan4; Yang, Jiayu4; Wang, Shibo5; Zhang, Han5; Li, Yao5,*; Zhang, Long2,5,*

Author Information

1Department of Painology, Shaoxing Second Hospital, Shaoxing, Zhejiang Province, China

2Center for Rehabilitation Medicine, Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, China

3Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

4Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi Province, China

5Institute for Smart Biomedical Materials, School of Materials Science & Engineering, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China

*Correspondence to: Long Zhang, MD, zhanglong@hmc.edu.cn; Yao Li, PhD, liyao@zstu.edu.cn

Funding:This work was supported by the Zhejiang Province Chinese Medicine Science and Technology Plan (No. 2025ZX284), Shaoxing Health Science and Technology Program (No. 2024SKY093), Clinical Research Fund of Pain Physician Branch of Zhejiang Medical Association (No. YS2024-50-010) and Shanxi Province Key Research and Development Program (No. ZJ2024104).

Abstract

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.

摘要

环境气体分子通过差异化的生物学效应广泛参与人体生理和病理调控。基于气体递质的治疗策略作为一种新兴的干预方式，在椎间盘退变管理中展现出显著的转化价值。椎间盘因其独特的无血管特性和复杂的生物力学微环境而易发进行性退变病理，而传统疗法存在疗效局限且具有侵入性风险。本综述系统梳理了气体疗法在椎间盘退变中的创新应用，涵盖临床已确立的臭氧和高压氧疗法，以及处于临床前阶段的氢气、硫化氢和一氧化氮干预措施。通过综合分析探讨了其分子特性、生物学功能及作用机制。现有证据表明，气体疗法通过靶向调控氧化应激-炎症-凋亡级联反应和细胞外基质代谢紊乱，显著缓解疼痛并改善功能障碍。其微创精准递送能力和多模态生物调节优势，为椎间盘退变提供了突破性的诊疗策略，展现出明确的临床转化潜力。