Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, People's Republic of China.
Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, People's Republic of China; Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an 710038, People's Republic of China.
Pain Physician. 2017 Jul;20(5):E673-E685.
In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available.
This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain.
Experimental trial in rats.
Institute for Biomedical Sciences of Pain.
By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively.
(1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (< 48 hours) inhibiting or antagonizing at Nav1.8 (A-803467), CXCR4 (AMD3100), mTOR (rapamycin), and histone deacetylase (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain.
Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not performed.
In the present study, we provided a line of evidence for the first time that IVF injection of ozone selectively relieved neuropathic pain but not inflammatory pain, and enhanced the analgesic effect of gabapentin.
Chronic pain, neuropathic pain, inflammatory pain, ozone therapy, interventional therapy, gabapentin, spared nerve injury, bee venom, complete Freud's adjuvant.
在中国南方一家医院进行的为期 5 年的随访研究表明，在受累节段水平行椎间孔臭氧注射可显著缓解慢性、难治性带状疱疹后神经痛患者的阵发性自发性疼痛和机械性痛觉过敏，并改善生活质量。然而，迄今为止，动物体内尚无概念验证研究。
本研究旨在探讨椎间孔臭氧对神经病理性和炎症性疼痛动物模型是否具有镇痛作用。
大鼠实验性试验。
疼痛生物医学研究所。
通过椎间孔注射，分别向正常、蜂毒或完全弗氏佐剂诱导的炎症性疼痛状态和 spared 神经损伤诱导的神经病理性疼痛状态的雄性 Sprague-Dawley 大鼠注射 50µl 含有 30µg/ml 臭氧-氧气混合物或 50µl 空气。评价椎间孔臭氧对疼痛相关行为的影响持续 2 周或 1 个月。然后，在臭氧治疗后 5 天通过腹腔内给予加巴喷丁（100mg/1kg 体重），评估其在神经病理性疼痛大鼠中的联合应用。最后，通过椎间孔注射，分别评价另外 4 种药物（AMD3100，一种 CXCR4 拮抗剂；A-803467，一种选择性 Nav1.8 阻滞剂；雷帕霉素，一种 mTOR 抑制剂；以及 MGCD0103，一种选择性组蛋白去乙酰化酶抑制剂）的长期镇痛效果。
（1）L4-5 椎间孔臭氧注射仅对神经病理性疼痛大鼠的机械性痛觉过敏有抑制作用，而对炎症性疼痛大鼠无作用；（2）与抑制或拮抗 Nav1.8（A-803467）、CXCR4（AMD3100）、mTOR（雷帕霉素）和组蛋白去乙酰化酶（MGCD0103）的其他选择性分子靶标药物（<48 小时）相比，椎间孔臭氧的镇痛作用持续时间更长（>14 天）；（3）在神经病理性疼痛大鼠中，联合应用全身给予加巴喷丁和椎间孔臭氧产生协同镇痛作用。
未评估臭氧足底注射的可能镇痛效果。
本研究首次提供了证据表明，椎间孔臭氧注射选择性缓解神经病理性疼痛而不缓解炎症性疼痛，并增强了加巴喷丁的镇痛效果。
慢性疼痛；神经病理性疼痛；炎症性疼痛；臭氧治疗；介入治疗；加巴喷丁； spared 神经损伤；蜂毒；完全弗氏佐剂。
Zotero 插件