Effects of intrathecal administration of nitric oxide synthase inhibitors on carrageenan-induced thermal hyperalgesia
Effects of intrathecal administration of nitric oxide synthase inhibitors on carrageenan-induced thermal hyperalgesia
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DOI：
10.1038/sj.bjp.0702508
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发表时间：
1999-04-01
影响因子：
7.3
通讯作者：
Coderre, TJ
中科院分区：
文献类型：
--
作者：
Osborne, MG;Coderre, TJ
1我们研究了各种一氧化氮合酶（NOS）抑制剂对角叉菜胶诱导的热痛觉过敏的影响。2首先，我们确定了时间Feint在皮下足底注射角叉菜胶到大鼠后爪产生最大的热痛觉过敏。随后，我们证明了鞘内给予非选择性NOS抑制剂L-N-G-硝基精氨酸甲酯（L-NAME）产生剂量依赖性的角叉菜胶诱导的热痛觉过敏的减少。3然后测试了四种相对选择性NOS抑制剂在减少角叉菜胶诱导的热痛觉过敏方面的功效。首先，检查了用神经元[7-硝基吲唑（7-NI）和3-溴-7-硝基吲唑（3-Br）]和诱导型[氨基胍（AG）和2-氨基-5，6-二氢-甲基噻嗪（AMT）] NOS抑制剂的延长治疗的效果。在由足底注射角叉菜胶引起的炎症过程中，并且在角叉菜胶后6小时使用足底装置测量热痛觉过敏。4当与载体处理相比时，除了7-NI之外，所有抑制剂都有效地减弱角叉菜胶诱导的热痛觉过敏。5最后，检查了早期和晚期给予神经元和诱导型NOS抑制剂对角叉菜胶诱导的热痛觉过敏的影响。我们发现，当在角叉菜胶炎症的早期阶段给药时，3-Br和AG都不显著影响热痛觉过敏，而当在损伤的晚期阶段给药时，只有AG能够减少热痛觉过敏。6我们的结果表明，诱导型NOS仅在角叉菜胶诱导的炎症反应的晚期阶段有助于热痛觉过敏，而神经元NOS可能在损伤的整个时间过程中起作用。
1 We examined the effects of various nitric oxide synthase (NOS) inhibitors on carrageenan-induced thermal hyperalgesia.2 First, we determined the time Feint at which a subcutaneous plantar injection of carrageenan into the rat hindpaw produced maximum thermal hyperalgesia. Subsequently, we demonstrated that intrathecal administration of the non-selective NOS inhibitor L-N-G-nitro-arginine methyl ester (L-NAME) produces a dose-dependent reduction of carrageenan-induced thermal hyperalgesia,3 Four relatively selective NOS inhibitors were then tested for their efficacy at reducing carrageenan-induced thermal hyperalgesia. Initially, the effects of prolonged treatment with inhibitors of neuronal [7-nitroindazole (7-NI) and 3-bromo-7-nitroindazole (3-Br)] and inducible [aminoguanidine (AG) and 2-amino-5,6-dihydro-methylthiazine (AMT)] NOS were examined, All agents were injected three times intrathecally during the course of inflammation caused by the plantar injection of carrageenan, and thermal hyperalgesia was measured at 6 h post-carrageenan using a plantar apparatus.4 All inhibitors, except for 7-NI, were effective at attenuating the carrageenan-induced thermal hyperalgesia when compared with vehicle treatment.5 Finally, the effects of early versus late administration of neuronal and inducible NOS inhibitors on carrageenan-induced thermal hyperalgesia were examined. We found that neither 3-Br nor AG significantly affected thermal hyperalgesia when administered during the early phase of carrageenan inflammation, while only AG was able to reduce thermal hyperalgesia when administered during the late phase of the injury.6 Our results suggest that inducible NOS contributes to thermal hyperalgesia in only the late stages of the carrageenan-induced inflammatory response, while neuronal NOS likely plays a role throughout the entire time course of the injury.