Effects of nitric oxide on pain perception by primary afferent neurons in inflammation

一氧化氮对炎症中初级传入神经元疼痛感知的影响

• 批准号: 11671840
• 负责人: MAEDA Sadaaki
• 金额: $ 2.3万
• 依托单位: Setsunan University (2000)Osaka University (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671840/
• 关键词: imflammation; cultured trigeminal ganglion cell; nitric oxide; bradykinin; pain; intracellular calcium; writhing reaction

In primary cultured trigeminal ganglion cells, NOC12, a nitric oxide (NO) donor, potentiated bradykinin (BK)-induced increase in intracellular free calcium concentration ([Ca^<2+>]i). The effect of NOC12 was blocked by carboxy-PTIO (specific NO radical scavenger) and ODQ (guanylate cyclase inhibitor), but not super oxide dismutase. 8-Bromo-cGMP potentiated the rise of [Ca^<2+>]i induced by BK.Both NOC12 and 8-bromo-cGMP did not affect the increase in [Ca^<2+>]i by histamine and carbachol. These results indicate that NO potentiates BK-induced increase in [Ca^<2+>]i by the activation of guanylate cyclase. This also suggests that NO may affect BK-mediated nociceptive responses.We investigated the effect of NO on kaolin-induced writhing behavior mediated by BK receptors. Intraperitoneal administration of lipopolysaccharide (LPS) in mice increase kaolin-induced writhing reaction, which was inhibited by BK-B2 receptor agonist Hoe140. The increase was inhibited by 2-iminopiperidine, an inducible NO synthase inhibitor. LPS-activated macrophages produced NO in a dose- and time-dependent manner. Pretreatment with 2-iminopiperidine caused a reduction in LPS-stimulated production of NO by peritoneal macrophages. These results indicate that LPS potentiated kaolin-induced writhing through producing NO.These results suggest that nitric oxide may potentiate pain perception in inflammation.

在原代培养的三叉神经节细胞中，一氧化氮（NO）供体NOC 12增强缓激肽（BK）诱导的细胞内游离钙浓度（[Ca^2+]i）的增加。特异性NO自由基清除剂（carboxy-PTIO）和鸟苷酸环化酶抑制剂（ODQ）可阻断NOC 12的作用，但超氧化物歧化酶（SOD）不能阻断NOC 12的作用。8-Bromo-cGMP可增强BK引起的[Ca^2+]i升高，而NOC 12和8-Bromo-cGMP对组胺和卡巴胆碱引起的[Ca^2+]i升高无影响。这些结果表明，NO通过激活鸟苷酸环化酶增强BK诱导的[Ca^2+]i增加。本实验研究了NO对BK受体介导的大鼠扭体反应的影响。腹腔注射脂多糖（LPS）可增加高岭土引起的小鼠扭体反应，此反应可被BK-B2受体激动剂Hoe 140抑制。2-亚氨基哌啶，诱导型NO合酶抑制剂抑制的增加。LPS激活的巨噬细胞以剂量和时间依赖性方式产生NO。用2-亚氨基哌啶预处理引起LPS刺激的腹腔巨噬细胞产生NO的减少。这些结果表明，LPS通过产生NO来增强高岭土引起的扭体反应。这些结果表明，一氧化氮可能增强炎症中的疼痛感知。

项目成果

山田隆史: "一次知覚神経終末における痛みの受容に対する一酸化窒素の作用"大阪大学歯学雑誌. 44巻1号. 1-12 (1999)

Takashi Yamada：“一氧化氮对初级感觉神经末梢疼痛接收的影响”大阪大学牙科杂志，第 44 卷，第 1. 1-12 期（1999 年）。

山田隆史: "一次知覚神経終末における痛みの受容に対する一酸化窒素の作用"大阪大学歯学雑誌. 44巻1号. 1-13 (1999)

Takashi Yamada：“一氧化氮对初级感觉神经末梢疼痛接收的影响”，大阪大学牙科杂志，第 44 卷，第 1. 1-13 期（1999 年）。

Yamada, T.: "Effects of nitric oxide on pain perception at primary afferent neurons"Journal of Osaka University Dental School (Japanese). 44(1). 1-13 (1999)

Yamada, T.：“一氧化氮对初级传入神经元疼痛感知的影响”大阪大学牙科学院学报（日语）。