Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain.

Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain.
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脊髓α-Amino-3-羟基-5-甲基-4-异恶唑丙酸受体受体的作用在完整的弗朗德辅助引起的炎症性疼痛中。

DOI:
10.1186/1744-8069-4-67
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发表时间:
2008-12-30
期刊:
影响因子:
3.3
通讯作者:
Tao YX
Tao YX
中科院分区:
医学3区
文献类型:
--
作者:
Park JS;Yaster M;Guan X;Xu JT;Shih MH;Guan Y;Raja SN;Tao YX

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脊髓α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)介导伤害性和非伤害性信息的急性脊髓加工,但其激活是否以及如何促进持续性炎性疼痛的中枢敏感化仍不清楚。在这里,我们研究了脊髓AMPAR在完全弗氏佐剂(CFA)诱导的持续性炎症疼痛的发展和维持中的作用。鞘内应用两种选择性非竞争性AMPAR拮抗剂CFM-2(25和50 μg)和GYKI 52466(50 μg),在CFA注射后2和24 h显著减弱了同侧后爪的机械和热超敏反应。CFM-2和GYKI 52466均不影响对侧对热刺激和机械刺激的基础反应。任何给药动物的自发活动均未改变。CFA诱导的炎症没有改变AMPAR亚基GluR 1和GluR 2在背角的总表达或分布,但改变了它们的亚细胞分布。注射CFA后24 h(而不是2 h),同侧L4-5背角的GluR 2在粗胞液组分中显著增加,在粗膜组分中显著减少。相反,在CFA注射后24 h(但不是2 h),同侧L4-5背角的粗胞质组分中GluR 1水平显著降低,粗膜组分中GluR 1水平升高。这些结果表明,脊髓AMPAR可能参与了持续性炎性疼痛的中枢脊髓机制。
Spinal cord α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA)-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg) and GYKI 52466 (50 μg), significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.
DOI: 10.1016/j.neuron.2006.02.027
发表时间: 2006-04-06
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影响因子: 16.2
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