Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice.
Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice.
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DOI：
10.1186/1744-8069-3-29
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发表时间：
2007-10-08
期刊：
影响因子：
3.3
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Guan Y;Yaster M;Raja SN;Tao YX
神经元一氧化氮合酶（nNOS）是神经元组织产生一氧化氮的关键酶，在炎症性疼痛中参与脊髓中枢致敏。然而，nNOS在神经性疼痛中的作用尚不清楚。本研究结合遗传策略和药理学方法，研究了nNOS基因敲除和药理学抑制对小鼠单侧第五腰椎神经损伤引起的神经性疼痛的影响。与野生型小鼠相比，nNOS敲除小鼠没有表现出神经损伤引起的机械超敏反应。此外，非特异性NOS抑制剂l - ng -硝基精氨酸甲酯（l - ng - nitroarginine methyl ester）腹腔（100 mg/kg）或鞘内（30 μg/5 μl）均可显著逆转野生型小鼠神经损伤后第7天神经损伤引起的机械超敏反应。鞘内注射选择性nNOS抑制剂7-硝基茚唑（8.15 μg/5 μl）也能显著减轻神经损伤引起的机械超敏反应。Western blot分析显示，神经损伤后第7天，nNOS蛋白在同侧L5背根神经节中表达显著升高，而在同侧L5腰椎中表达不明显。神经损伤后，诱导型NOS和内皮型NOS蛋白在脊髓和背根神经节的表达均无明显变化。我们的研究结果表明，nNOS，特别是在背根神经节，可能参与神经损伤后机械性超敏反应的发展和/或维持。
Neuronal nitric oxide synthase (nNOS) is a key enzyme for nitric oxide production in neuronal tissues and contributes to the spinal central sensitization in inflammatory pain. However, the role of nNOS in neuropathic pain remains unclear. The present study combined a genetic strategy with a pharmacologic approach to examine the effects of genetic knockout and pharmacologic inhibition of nNOS on neuropathic pain induced by unilateral fifth lumbar spinal nerve injury in mice. In contrast to wildtype mice, nNOS knockout mice failed to display nerve injury-induced mechanical hypersensitivity. Furthermore, either intraperitoneal (100 mg/kg) or intrathecal (30 μg/5 μl) administration of L-NG-nitro-arginine methyl ester, a nonspecific NOS inhibitor, significantly reversed nerve injury-induced mechanical hypersensitivity on day 7 post-nerve injury in wildtype mice. Intrathecal injection of 7-nitroindazole (8.15 μg/5 μl), a selective nNOS inhibitor, also dramatically attenuated nerve injury-induced mechanical hypersensitivity. Western blot analysis showed that the expression of nNOS protein was significantly increased in ipsilateral L5 dorsal root ganglion but not in ipsilateral L5 lumbar spinal cord on day 7 post-nerve injury. The expression of inducible NOS and endothelial NOS proteins was not markedly altered after nerve injury in either the dorsal root ganglion or spinal cord. Our findings suggest that nNOS, especially in the dorsal root ganglion, may participate in the development and/or maintenance of mechanical hypersensitivity after nerve injury.
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DOI：
10.1073/pnas.86.13.5159
发表时间：
1989-07-01
影响因子：
11.1
作者：
KNOWLES, RG;PALACIOS, M;MONCADA, S
通讯作者：
MONCADA, S
影响因子：
7.3
作者：
Osborne, MG;Coderre, TJ
通讯作者：
Coderre, TJ
影响因子：
7.4
作者：
Chu, YC;Guan, Y;Tao, YX
通讯作者：
Tao, YX
影响因子：
7.4
作者：
Khalil, Z;Khodr, B
通讯作者：
Khodr, B
影响因子：
3.3
作者：
CROSBY, G;MAROTA, JJA;HUANG, PL
通讯作者：
HUANG, PL