BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N₂O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N₂O concentration and the shortest time of N₂O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N₂O with gabapentin, a reference drug used in human neuropathic pain relief.METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats.RESULTS: Among the various N₂O concentrations tested, which ranged from 25% to 50%, only 50% N₂O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N₂O.CONCLUSIONS: These preclinical results suggest that N₂O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies.

中文翻译：

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一氧化二氮持续缓解神经性大鼠的疼痛超敏反应：剂量依赖性作用。

背景：尽管有许多药理学方法，但尚无常见的镇痛药能对大多数神经性疼痛患者产生有意义的缓解作用。尽管一氧化二氮（N ₂ O）是一种弱镇痛药，可通过阿片样物质依赖性机制起作用，但它还是N-甲基-D-天冬氨酸受体（NMDAR）的拮抗剂。目的：NMDAR在神经损伤引起的疼痛敏感性发展中起着至关重要的作用。目的：利用雄性大鼠坐骨神经的慢性压迫性损伤作为神经性疼痛的临床前模型，本研究的首要目的是评估神经痛。最低ñ ₂ ö浓度和N的最短时间₂o损伤后接触会持续缓解神经性疼痛。第二个目的是比较N ₂ O与加巴喷丁（一种用于人类神经性疼痛缓解的参考药物）的作用。方法：使用大鼠足底压力发声试验评估伤害感受性阈值的变化。结果：在各种N _2中所测试的O浓度范围为25％至50％，单次暴露1 h 15分钟仅50％N ₂ O会引起持续性（至少三周）疼痛显着降低（60％）。单一加巴喷丁剂量（75 mg / kg至300 mg / kg，腹膜内）诱发急性（1 h至1 h 30 min）剂量依赖性作用，但未产生如N ₂所观察到的持续作用O.结论：这些临床前结果表明，与人类使用的其他药物（如加巴喷丁类药物或NMDAR拮抗剂）相比，N ₂ O有利于坐骨神经损伤后的持久神经性疼痛缓解。本临床前研究为开展比较性临床研究提供了依据。