Zhao Wenjuan, Konno Ryuichi, Zhou Xiang-Jun, Yin Ming, Wang Yong-Xiang
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Cell Mol Neurobiol. 2008 Jun;28(4):581-91. doi: 10.1007/s10571-007-9200-y. Epub 2007 Sep 15.
(1). We investigated the effects of inhibiting D: -amino-acid oxidase (DAO) activity on nociceptive responses through the use of mutant ddY/DAO(-) mice, which lack DAO activity, and through the application of a selective inhibitor of DAO, sodium benzoate, in the tail flick test, hot-plate test, formalin test, and acetic acid-induced writhing test. (2). Compared with normal ddY/DAO+ mice, ddY/DAO(- )mice showed significantly prolonged tail withdrawal latency in the tail flick test and licking/jumping latency in the hot-plate test, as well as significantly reduced duration of licking/biting in the late phase of the formalin test and the number of abdominal writhing in the acetic acid-induced writhing test. (3). In addition, we investigated the effects of sodium benzoate in Kunming mice having normal DAO activity. (4). Intravenous administration of sodium benzoate (400 mg/kg) significantly inhibited pain responses of the late phase of the formalin test and abdominal writhing responses in the acetic acid-induced writhing test, with no effects on the early phase flinch responses in the formalin test, nociceptive responses in the tail flick test, or hot-plate test. (5). These results suggest that DAO acts as a pro-nociceptive factor in pain, particularly chronic pain, transmission and modulation, and may be a target for pain treatment.
(1). 我们通过使用缺乏D-氨基酸氧化酶（DAO）活性的突变型ddY/DAO(-)小鼠，并在甩尾试验、热板试验、福尔马林试验和醋酸诱导扭体试验中应用DAO的选择性抑制剂苯甲酸钠，研究了抑制DAO活性对伤害性反应的影响。(2). 与正常的ddY/DAO+小鼠相比，ddY/DAO(-)小鼠在甩尾试验中的甩尾潜伏期和热板试验中的舔舐/跳跃潜伏期显著延长，在福尔马林试验后期的舔舐/咬噬持续时间以及醋酸诱导扭体试验中的腹部扭体次数显著减少。(3). 此外，我们研究了苯甲酸钠对具有正常DAO活性的昆明小鼠的影响。(4). 静脉注射苯甲酸钠（400mg/kg）显著抑制了福尔马林试验后期的疼痛反应和醋酸诱导扭体试验中的腹部扭体反应，对福尔马林试验早期的退缩反应、甩尾试验中的伤害性反应或热板试验没有影响。(5). 这些结果表明，DAO在疼痛，特别是慢性疼痛的传递和调节中作为一种促伤害性因子起作用，可能是疼痛治疗的一个靶点。
