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

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.