Various gases for the treatment of neuropathic pain: mechanisms, current status, and future perspectives

Liu, Yan1,#; Shen, Tianhao1,#; Li, Qiuying1; Yu, Xue1; Liu, Yu1; Zhou, Cheng1; Han, Ji2,*; Zhu, Yongqiang1,*

Author Information

1Department of Intervention, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

2Department of Traditional Chinese Medicine Internal Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

*Correspondence to: Yongqiang Zhu, MD, pt10840@shutcm.edu.cn; Ji Han, doctorhanji@126.com.

#Both authors contributed equally to this work.

Funding:This work was supported by Shanghai Municipal Health Commission Youth Talent Program, No. 2022YQ037 (to YL); Research Startup Project for Talent Introduction in Shanghai Putuo District, No. 2024-YJRC-05 (to YZ); Key Specialized Disease Project in Putuo District, Shanghai, No. 2024tszb04 (to YZ)

Abstract

In recent years, medical gas therapy has emerged as a promising approach for treating neuropathic pain. This review article aimed to investigate the therapeutic effects of medical gas therapy on neuropathic pain and its underlying mechanisms, thereby providing a theoretical foundation for clinical practice. A literature search was conducted using the Web of Science Core Collection database. Co-occurrence analysis of keywords revealed that terms including “neuropathic pain,” “nitric oxide,” “nitric oxide synthase,” “pain,” and “ozone” frequently appeared. Cluster analysis grouped these keywords into four primary categories: intervertebral disc disease and gas therapy, mechanisms of neuropathic pain and gas interventions, the role of nitric oxide in modulating neuropathic pain and gas therapy, and the effects of gas therapy on mental disorders in the context of neuropathic pain treatment. The analysis of highly cited literature in the field of medical gas therapy for neuropathic pain emphasizes the crucial roles of nitric oxide and nitric oxide synthase in nerve injury and pain. Various types of gas therapy, including oxygen-ozone therapy and nitric oxide-related therapies, show promise in treating pain following peripheral nerve injury. Oxidative stress and nitric oxide are crucial regulatory factors in the pain signaling associated with trigeminal neuralgia. Ozone therapy alleviates trigeminal pain by inhibiting inflammatory responses, reducing oxidative stress, and modulating neurotransmitter release. Novel nanomaterials, such as manganese oxide nanoparticles, have also demonstrated potential in scavenging free radicals and alleviating sciatic nerve pain. Ozone therapy has shown good clinical efficacy in treating lumbar disc herniation and sciatica, whereas both ozone therapy and hyperbaric oxygen therapy have demonstrated effectiveness and safety in managing postherpetic neuralgia. In conclusion, medical gas therapy for neuropathic pain primarily includes oxygen-ozone therapy, nitric oxide-related therapies, hydrogen sulfide-related therapies, and hyperbaric oxygen therapy. While these therapies exhibit efficacy in managing neuropathic pain, further research is necessary to elucidate their mechanisms of action and safety profiles. Although hyperbaric oxygen therapy and ozone therapy have already been implemented in clinical research, other types of gas therapy are still in the animal testing phase. Therefore, future studies should focus on conducting more multicenter, large-sample randomized controlled trials to accelerate clinical translation and provide more effective treatment options for patients suffering from neuropathic pain.

摘要

近年来，医用气体疗法已成为治疗神经病理性疼痛的一种有前景的方法。本综述旨在研究医用气体疗法对神经病理性疼痛的治疗效果及其潜在机制，从而为临床实践提供理论依据。通过Web of Science核心合集数据库进行文献检索。关键词共现分析显示，"神经病理性疼痛"、"一氧化氮"、"一氧化氮合酶"、"疼痛"和"臭氧"等词条出现频率较高。聚类分析将这些关键词归纳为四个主要类别：椎间盘疾病与气体疗法、神经病理性疼痛的机制与气体干预、一氧化氮在调节神经病理性疼痛及气体疗法中的作用，以及气体疗法在治疗神经病理性疼痛时对精神障碍的影响。对医用气体疗法治疗神经病理性疼痛领域高被引文献的分析强调了—氧化氮和一氧化氮合酶在神经损伤和疼痛中的关键作用。多种类型的气体疗法，包括臭氧氧疗和一氧化氮相关疗法，在治疗周围神经损伤后疼痛方面显示出潜力。氧化应激和一氧化氮是三叉神经痛相关疼痛信号通路中的关键调节因子。臭氧疗法通过抑制炎症反应、减轻氧化应激和调节神经递质释放来缓解三叉神经痛。新型纳米材料，如氧化锰纳米颗粒，也显示出清除自由基和缓解坐骨神经痛的潜力。臭氧疗法在治疗腰椎间盘突出症和坐骨神经痛方面显示出良好的临床疗效，而臭氧疗法和高压氧治疗在管理带状疱疹后神经痛方面均显示出有效性和安全性。总之，用于治疗神经病理性疼痛的医用气体疗法主要包括臭氧氧疗、一氧化氮相关疗法、硫化氢相关疗法和高压氧治疗。尽管这些疗法在控制神经病理性疼痛方面显示出疗效，但仍需进一步研究阐明其作用机制和安全性。虽然高压氧治疗和臭氧疗法已在临床研究中得到应用，但其他类型的气体疗法仍处于动物试验阶段。因此，未来的研究应侧重于开展更多多中心、大样本随机对照试验，以加速临床转化，为神经病理性疼痛患者提供更有效的治疗选择。