Changes in the effect of spinal prostaglandin E2 during inflammation:: Prostaglandin E (EP1-EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint
Changes in the effect of spinal prostaglandin E2 during inflammation:: Prostaglandin E (EP1-EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint
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DOI：
10.1523/jneurosci.0882-03.2004
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发表时间：
2004-01-21
影响因子：
5.3
通讯作者：
Ebersberger, A
中科院分区：
文献类型：
--
作者：
B채r, KJ;Natura, G;Ebersberger, A
炎性疼痛是由外周和中枢伤害感受神经元的敏化引起的。前列腺素实质上有助于神经元敏化在这两个网站。前列腺素E-2（PGE（2））应用于脊髓引起神经元过度兴奋，类似于外周炎症。由于PGE（2）可以通过EP 1-EP 4受体发挥作用，我们探讨了脊髓中这些受体在脊髓过度兴奋发展中的作用。记录从伤害性背角神经元与膝关节的主要输入，和神经元的反应，以伤害性和无害性刺激的膝，踝关节，和爪子进行了研究后，脊髓应用最近开发的特定的EP 1-EP 4受体激动剂。在正常情况下，脊髓应用EP 1、EP 2和EP 4受体激动剂可诱导与PGE相似的脊髓过度兴奋（2）。有趣的是，脊髓EP受体激活的作用在关节炎症过程中发生了变化。当膝关节在记录前7-11小时发炎时，只有EP 1受体的激活引起额外的易化，而EP 2和EP 4受体激动剂的脊柱应用没有影响。此外，EP 3 α受体激动剂降低了对机械刺激的反应。后者还减弱了脊髓PGE诱导的脊髓过度兴奋（2）。在分离的DRG神经元中，EP 3 α激动剂降低了PGE（2）对TTX抗性钠电流的易化作用。因此，脊髓PGE（2）的原伤害感受效应可能受到限制，特别是在炎症条件下，通过激活EP 3受体的抑制性剪接变体。后者可能是一个有趣的目标，控制脊髓过度兴奋的炎症疼痛状态。
Inflammatory pain is caused by sensitization of peripheral and central nociceptive neurons. Prostaglandins substantially contribute to neuronal sensitization at both sites. Prostaglandin E-2 (PGE(2)) applied to the spinal cord causes neuronal hyperexcitability similar to peripheral inflammation. Because PGE(2) can act through EP1-EP4 receptors, we addressed the role of these receptors in the spinal cord on the development of spinal hyperexcitability. Recordings were made from nociceptive dorsal horn neurons with main input from the knee joint, and responses of the neurons to noxious and innocuous stimulation of the knee, ankle, and paw were studied after spinal application of recently developed specific EP1-EP4 receptor agonists. Under normal conditions, spinal application of agonists at EP1, EP2, and EP4 receptors induced spinal hyperexcitability similar to PGE(2). Interestingly, the effect of spinal EP receptor activation changed during joint inflammation. When the knee joint had been inflamed 7-11 hr before the recordings, only activation of the EP1 receptor caused additional facilitation, whereas spinal application of EP2 and EP4 receptor agonists had no effect. Additionally, an EP3alpha receptor agonist reduced responses to mechanical stimulation. The latter also attenuated spinal hyperexcitability induced by spinal PGE(2). In isolated DRG neurons, the EP3alpha agonist reduced the facilitatory effect of PGE(2) on TTX-resistant sodium currents. Thus pronociceptive effects of spinal PGE(2) can be limited, particularly under inflammatory conditions, through activation of an inhibitory splice variant of the EP3 receptor. The latter might be an interesting target for controlling spinal hyperexcitability in inflammatory pain states.