本文章来自上海长征医院麻醉科袁红斌教授课题组（该组已经发表氢气相关论文3篇，分别是关于小肠缺血、脊髓创伤和疼痛方面），是关于氢气与疼痛关系的研究，已经被Brain res接受。也是国内氢气领域在国际上发表的第19篇论文和第17篇论著（日本现在是18篇）。

活性氧参与神经病理性和炎症性疼痛的发生与发展。氢气可通过减少活性氧发挥对心脏、肝脏等器官缺血再灌注损伤的保护作用。本研究提出并验证氢气能减轻神经病理性疼痛的假说，采用慢性压迫性疼痛模型，在模型制备前1天和后7天通过椎管内连续给含氢气生理盐水。我们研究发现，含氢气生理盐水能显著提高神经病理性疼痛的痛阈，能降低模型第14天后脊髓中MPO、MDA和蛋白羰基化产物，而且能抑制p38 MAPK和BDNF的表达，但对ATP 受体P2X4R表达没有明显影响。研究提示，椎管内给含氢气生理盐水能通过抑制氧化应激和p38 MAPK和BDNF的表达发挥提高动物神经病理性疼痛痛阈的作用。

氢气抗氧化目前最主要的发现是对组织器官的缺血和炎症具有明显对抗作用，这种作用与氢气的抗氧化作用关系密切。实际上人类的许多疾病都与氧化损伤关系十分密切，例如影响人类健康的最常见疾病高血压、糖尿病、动脉硬化、肿瘤、心脑血管疾病、创伤、肾脏和肝脏功能异常等，都与氧化损伤有关。神经系统疾病除了急性损伤和慢性退行性改变以外，疼痛也是一大类影响人类健康的重要疾病，尽管人类对疼痛的研究有非常长的历史，也找到许多能治疗和缓解疼痛的药物和手段，但仍存在许多问题没有克服，例如成隐性、耐受性、对其他器官毒性作用等问题，因此一直是人们十分关注的课题。人们一直希望能找到有效而副作用小的镇痛物质，最近几年，人们逐渐重视炎症和氧化应激在疼痛发生发展中的重要作用，已经成为该领域的一个研究热点。氢气抗氧化和抗炎症作用的发现，给人一种新的提示，也许氢气是我们寻找的理想镇痛物质。但是，疼痛的机制非常复杂，单独使用氢气恐怕难以实现目前，更有可能的是把氢气与其他一些药物和手段的联合使用，在降低药物副作用，维持疗效或预防疼痛发生中具有更大的意义。

点评：尽管本研究初步证明氢气的镇痛作用，并初步观察了抗氧化与细胞信号分子的改变，但是其作用的强度、作用的细胞机制、甚至是否确定与抗氧化和这些信号分子的关系都非常不明确。因此，尽管该研究首先研究了氢气的镇痛作用，非常有新意。但研究这个课题的详细过程仍需要大量的工作去作。例如，这种作用的细胞类型，是神经细胞还是其他细胞，是通过炎症抑制还是通过细胞功能调节，是什么细胞途径发挥重要作用，甚至是否影响经典的细胞外激素或神经调节物质等等。这些都是值得考虑的问题。

Hydrogen-rich saline attenuated neuropathic pain by reducing oxidative stress and BDNF in spinal cord in a chronic constriction injury rat model pdf

QIAN-BO CHEN^1*, CHENG-WEN CHEN^1*, SHUANG-QIONG ZHOU¹, XIAO-DI YAN¹, XUE-YIN SHI¹, JOHN H. ZHANG², CHUN-YAN XIA³, WEI ZHANG⁴, HONG-BIN YUAN¹, & XUE-JUN SUN⁴

Department of Anesthesiology¹, Changzheng Hospital, Second Military Medical University, Shanghai, PR China; Department of Neurosurgery², Loma Linda University, Loma Linda, California, CA, USA; Department of Pathology³, Changzheng Hospital, Second Military Medical University, Shanghai, PR China; Department of Diving Medicine⁴, Faculty of Naval Medicine, Second Military Medical University, Shanghai, PR China.

*Qianbo Chen and Chengwen Chen contributed equally to this work

Correspondence to Dr. HONG-BIN YUAN, Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, PR China. Tel: (86)2181885822. Fax: (86)2163610109. E-mail: jfjczyy@yahoo.cn

Dr. Xuejun Sun, Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, PR China. Tel:(86)2125070349.Fax:(86)2165492382.Email:sunxjk@hotmail.com

Abstract

Reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Hydrogen gas reduces reactive oxygen species and alleviates cerebral, myocardial, and hepatic ischemia/reperfusion injuries. In the present study, we tested the hypothesis that hydrogen-rich saline reduces neuropathic pain in a rat model of chronic constriction injury. Hydrogen-rich saline was administered by intrathecal injection in a dose of 100ul/kg once daily at before and 1-7 days after chronic constriction injury. We observed that hydrogen-rich saline increased significantly the mechanical thresholds of neuropathic pain when compared to vehicle (physiologic saline) treatment after chronic constriction injury. Hydrogen-rich saline decreased the leveled of myeloperoxidase (MPO), maleic dialdehyde (MDA), and protein carbonyl at 14th day in spinal cord after chronic constriction injury. In addition, hydrogen-rich saline suppressed the expression of p38 MAPK and brain-derived neurotrophic factor (BDNF) but not an ATP receptor P2X4R in the spinal cord. In conclusion, our observation suggested that intrathecal injection of hydrogen-rich saline decreased oxidative stress and the expression of p38MAPK and BDNF which may be responsible for the enhanced threshold of neuropathic pain in this chronic constriction injury rat model.

KEY WORDS: hydrogen-rich saline, brain-derived neurotrophic factor, p38MAPK, reactive oxygen species, chronic constriction injury