Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats provide no evidence of a role for nitric oxide in neuropathic mechanical allodynia
Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats provide no evidence of a role for nitric oxide in neuropathic mechanical allodynia
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DOI：
10.1016/j.neulet.2005.05.036
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发表时间：
2005-09-16
影响因子：
2.5
通讯作者：
Lodge, D
中科院分区：
文献类型：
--
作者：
Lee, DH;Singh, JP;Lodge, D
本文观察了非选择性一氧化氮合酶抑制剂L对结扎大鼠左侧L5、L6脊神经诱发机械性痛觉超敏前后的治疗作用。用von Frey细丝缩足的触觉阈值来衡量机械性超敏反应的程度。腹膜腔内(Ip)脊髓神经结扎后1周给予L-NAME(3~30 mg/kg)可剂量依赖性地减少机械性痛觉过敏的行为体征，但这种作用不被L-精氨酸(300 mg/kg)所逆转。N-奥米伽-硝基-L-精氨酸(L-NNA，ip，30 mg/kg)、氨基胍(AG，i.p，30 mg/kg)和一氧化氮合酶抑制剂(LY457963，ip，30 mg/kg)不能降低SNL大鼠的机械敏感性。此外，采用体外一氧化氮合酶活性测定，L-NAME部分抑制脊髓一氧化氮合酶活性，而LY457963几乎完全抑制脊髓一氧化氮合酶活性。脊髓神经结扎前30min预先给予L-NAME(30 mg/kg)或N-甲基-D-天冬氨酸受体拮抗剂MK-801(0.5 mg/kg)可明显预防长时间脊神经结扎后机械性超敏的发生。但大剂量L精氨酸(100 mg/kg或300 mg/kg，ip)不能逆转L的超前效应。以上结果提示，L-NAME的抗痛觉超敏和阻断作用均不是通过抑制一氧化氮合酶介导的。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
We have investigated the effect of treatment with N-omega-nitro-L-arginine methylester (L-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both before and after the induction of mechanical allodynia by tight ligation of the left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical allodynia was measured by tactile threshold for paw flinching with von Frey filaments. Intraperitoneal (i.p.) administration of L-NAME (3-30 mg/kg) 1 week after the spinal nerve ligation produced a dose-dependent reduction of the behavioral signs of mechanical allodynia, but the effect was not reversed by pretreatment with L-arginine (300 mg/kg). N-omega-Nitro-L-arginine (L-NNA, i.p., 30 mg/kg), aminoguanidine (AG, i.p., 30 mg/kg) and a potent neuronal NOS inhibitor (LY457963, i.p., 30 mg/kg) did not reduce mechanical sensitivity in the SNL rats. Furthermore, using an ex vivo NOS activity assay, L-NAME partially inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited the spinal NOS activity. Prior administration of L-NAME (i.p., 30 mg/kg) or of MK-801 (0.5 mg/kg), an NMDA antagonist, 30 min before the spinal nerve ligation significantly prevented the development of mechanical allodynia after spinal nerve ligation for an extended period of time. High doses of L-arginine (100 mg/kg or 300 mg/kg, i.p.), however, did not reverse the preemptive effect of L-NAME. These results suggest that neither the anti-allodynic nor the preemptive effects of L-NAME are mediated by NOS inhibition. (c) 2005 Elsevier Ireland Ltd. All rights reserved.