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Logo of neuroscibullNeuroscience Bulletin
Neurosci Bull. 2010 June; 26(3): 211–218.
Published online 2010 June 3. doi:  10.1007/s12264-010-0127-9
PMCID: PMC5552487

Language: English | Chinese

Effects of multiple intrathecal administration of L-arginine with different doses on formalin-induced nociceptive behavioral responses in rats




To investigate the effects of nitric oxide (NO) with different doses on modulation of inflammatory pain, and its possible mechanisms.


NO precursor L-arginine (L-Arg) was intrathecally administered in rats at a dose of 10 μg per day (low dose group) or 250 μg per day (high dose group) for a succession of 4 d. Normal saline was applied as a control. Then the rats were subcutaneously injected with formalin (100 μL, 2%) into the right hindpaw, and the nociceptive behavioral responses within 1 h were observed. At 4 h after formalin injection, neuronal NO synthase (nNOS) and c-Fos expression in spinal dorsal horn was examined with immunocytochemistry method.


The subcutaneous injection of formalin evoked biphasic behaviors of licking or biting the injected paw. There was no difference in acute phase of formalin test among the 3 groups, while in tonic phase, the licking and biting time, and the protein levels of nNOS and c-Fos in spinal dorsal horn were significantly decreased in low dose group and increased in high dose group, compared with those in control group.


These results suggest that multiple administration of NO with different doses may produce different effects. On one hand, the low dose of NO can induce antinociception. On the other hand, the high dose of NO can induce pronociception.

Keywords: L-arginine, nitric oxide, formalin test, pain, nitric oxide synthase, genes, c-fos, spinal cord





大鼠鞘内每天注入一氧化氮的前体左旋精氨酸(L-Arg)10 μg (低剂量组), 250 μg(高剂量组)或生理盐水(对照组), 共持续4天。 随后在大鼠右后爪掌皮下注射2%甲醛溶液(100 μL), 并在之后的1h 内观察大鼠舔咬后爪的痛行为反应, 4h 后用免疫细胞化学技术检测大鼠脊髓背角c-Fos蛋白和神经元型一氧化氮合酶(nNOS)的表达。


福尔马林引起的大鼠舔咬后爪的痛行为反应有两个时相。 第一相的急性痛行为反应在各组间无明显差异。 对于第二相的慢性痛行为反应累计时间以及脊髓背角c-Fos 和nNOS 的表达水平, 低剂量组较对照组显著降低, 而高剂量组较对照组显著升高。


不同剂量的一氧化氮对脊髓痛觉的调制作用具有双面性, 小剂量具有镇痛作用而大剂量具有促痛作用。

关键词: L-精氨酸, 一氧化氮, 福尔马林试验, 痛觉, 一氧化氮合酶, 基因, c-fos, 脊髓


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