NITRIC-OXIDE MEDIATES ALLODYNIA INDUCED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) OR PROSTAGLANDIN-F2-ALPHA IN CONSCIOUS MICE
NITRIC-OXIDE MEDIATES ALLODYNIA INDUCED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) OR PROSTAGLANDIN-F2-ALPHA IN CONSCIOUS MICE
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DOI：
10.1016/0304-3959(94)00183-f
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发表时间：
1995-05-01
期刊：
影响因子：
7.4
通讯作者：
HAYAISHI, O
中科院分区：
文献类型：
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作者：
MINAMI, T;NISHIHARA, I;HAYAISHI, O
我们最近报道，在清醒小鼠中鞘内（i.t.）注射前列腺素（PG）E（2）或PGF（2α）可通过包括谷氨酸受体系统在内的途径诱导异常性疼痛。 PGE(2) 和 PGF(2α) 诱发的异常性疼痛分别被 NMDA 和代谢型谷氨酸受体亚型拮抗剂阻断。在本研究中，我们检查了一氧化氮 (NO) 参与 PG 诱发的异常性疼痛的可能性。通过用画笔轻轻抚摸小鼠的胁腹来每 5 分钟评估一次异常性疼痛。在清醒的小鼠中鞘内注射 L-精氨酸（一氧化氮合酶（NOS）的底物）会导致异常性疼痛。 L-精氨酸对异常性疼痛的剂量依赖性显示出钟形模式（1-10μg/小鼠）。在it后10-15分钟观察到5.0μg的最大异常性疼痛效果。注射，在时间过程和强度上与 L-谷氨酸诱导的相似。 NOS 抑制剂 N omega-硝基-L-精氨酸甲酯 (L-NAME) 和可溶性鸟苷酸环化酶抑制剂亚甲蓝可剂量依赖性地减少 L-精氨酸引起的异常性疼痛，IC50 值分别为 7.68 和 8.70 pg/小鼠。 PGE(2) 诱导的异常性疼痛也受到 L-NAME 和亚甲蓝的剂量依赖性抑制，IC50 值为 94.7 和 74.9 pg/小鼠。 PGF(2α) 诱导的异常性疼痛可被亚甲蓝抑制，IC50 值为 40.6 pg/小鼠，但 L-NAME 在剂量高达 1.0 ng 时则不能抑制。这些结果表明，PGE(2)诱导的异常性疼痛是通过NO生成系统介导的，并且PGF(2α)诱导的异常性疼痛可能是通过与脊髓中不同于NO生成位点的NO系统相互作用来介导的。
We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) E(2) or PGF(2 alpha) in conscious mice induced allodynia through a pathway that includes the glutamate receptor system. Allodynia induced by PGE(2) and PGF(2 alpha) was blocked by antagonists for NMDA and metabotropic glutamate receptor subtypes, respectively, In the present study, we examined the possibility for the involvement of nitric oxide (NO) in the PG-evoked alodynia. Allodynia was assessed once every 5 min by light stroking of the flank of mice with a paintbrush. Intrathecal administration of L-arginine, a substrate of nitric oxide synthase (NOS), in conscious mice resulted in allodynia. Dose dependency of L-arginine for allodynia showed a bell-shaped pattern (1-10 mu g/mouse). The maximal allodynic effect was observed with 5.0 mu g at 10-15 min after i.t. injection, similar in time course and magnitude to that induced by L-glutamate. L-Arginine-induced allodynia was dose-dependently reduced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue with IC50 values of 7.68 and 8.70 pg/mouse, respectively. PGE(2)-induced allodynia was also dose-dependently inhibited by L-NAME and methylene blue with IC50 values of 94.7 and 74.9 pg/mouse. PGF(2 alpha)-induced allodynia was inhibited by methylene blue with an IC50 value of 40.6 pg/mouse, but not by L-NAME at doses up to 1.0 ng. These results demonstrate that PGE(2)-induced allodynia is mediated through the NO-generating system and that PGF(2 alpha)-induced allodynia may be mediated by interactions with the NO system at a site different from the NO-generating site in the spinal cord.