The spinal cord expression of neuronal and inducible nitric oxide synthases and their contribution in the maintenance of neuropathic pain in mice.
The spinal cord expression of neuronal and inducible nitric oxide synthases and their contribution in the maintenance of neuropathic pain in mice.
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DOI：
10.1371/journal.pone.0014321
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发表时间：
2010-12-13
期刊：
影响因子：
3.7
通讯作者：
Pol O
中科院分区：
文献类型：
--
作者：
Hervera A;Negrete R;Leánez S;Martín-Campos JM;Pol O
由神经元（NOS 1）、诱导型（NOS 2）或内皮型（NOS 3）一氧化氮合酶产生的一氧化氮有助于疼痛处理，但NOS 1和NOS 2在维持慢性周围神经病理性疼痛中的确切作用以及它们在野生型（WT）和NOS敲除（KO）脊髓中表达的可能代偿性变化，在全坐骨神经结扎后21天的小鼠仍然未知。在手术后1至21天，在WT、NOS 1-KO和NOS 2-KO小鼠中评价由坐骨神经损伤诱导的机械和热异常性疼痛以及热痛觉过敏。还评估了手术后21天WT和KO小鼠脊髓中NOS 1、NOS 2和NOS 3的mRNA和蛋白水平。与分别在NOS 1-KO和NOS 2-KO动物中观察到的消除的机械异常性疼痛和热痛觉过敏以及减少或抑制的热异常性疼痛相反，坐骨神经损伤导致WT小鼠中的神经病性综合征。坐骨神经损伤还分别增加WT和NOS 1-KO小鼠中NOS 1和NOS 2亚型的脊髓表达，但不增加NOS 3的表达。此外，需要NOS 2的存在来增加脊髓中NOS 1的表达，而增加的NOS 1表达可能避免神经损伤WT小鼠脊髓中NOS 2的上调。这些数据表明，增加脊髓表达的NOS 1，调节NOS 2，可能是负责维持慢性周围神经性疼痛的小鼠，并提出这些酶作为有趣的治疗靶点，为他们的治疗。
Nitric oxide generated by neuronal (NOS1), inducible (NOS2) or endothelial (NOS3) nitric oxide synthases contributes to pain processing, but the exact role of NOS1 and NOS2 in the maintenance of chronic peripheral neuropathic pain as well as the possible compensatory changes in their expression in the spinal cord of wild type (WT) and NOS knockout (KO) mice at 21 days after total sciatic nerve ligation remains unknown. The mechanical and thermal allodynia as well as thermal hyperalgesia induced by sciatic nerve injury was evaluated in WT, NOS1-KO and NOS2-KO mice from 1 to 21 days after surgery. The mRNA and protein levels of NOS1, NOS2 and NOS3 in the spinal cord of WT and KO mice, at 21 days after surgery, were also assessed. Sciatic nerve injury led to a neuropathic syndrome in WT mice, in contrast to the abolished mechanical allodynia and thermal hyperalgesia as well as the decreased or suppressed thermal allodynia observed in NOS1-KO and NOS2-KO animals, respectively. Sciatic nerve injury also increases the spinal cord expression of NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively. Moreover, the presence of NOS2 is required to increase the spinal cord expression of NOS1 whereas an increased NOS1 expression might avoid the up-regulation of NOS2 in the spinal cord of nerve injured WT mice. These data suggest that the increased spinal cord expression of NOS1, regulated by NOS2, might be responsible for the maintenance of chronic peripheral neuropathic pain in mice and propose these enzymes as interesting therapeutic targets for their treatment.