Ahmadi Seifollah, Lippross Sebastian, Neuhuber Winfried L, Zeilhofer Hanns U
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Emil-Fischer-Zentrum, Fahrstrasse 17, D-91054 Erlangen, Germany.
Nat Neurosci. 2002 Jan;5(1):34-40. doi: 10.1038/nn778.
Despite the crucial role that prostaglandins (PGs) have in the sensitization of the central nervous system to pain, their cellular and molecular targets leading to increased pain perception have remained elusive. Here we investigated the effects of PGE(2) on fast synaptic transmission onto neurons in the rat spinal cord dorsal horn, the first site of synaptic integration in the pain pathway. We identified the inhibitory (strychnine-sensitive) glycine receptor as a specific target of PGE(2). PGE(2), but not PGF(2 alpha), PGD(2) or PGI(2), reduced inhibitory glycinergic synaptic transmission in low nanomolar concentrations, whereas GABAA, AMPA and NMDA receptor-mediated transmission remained unaffected. Inhibition of glycine receptors occurred via a postsynaptic mechanism involving the activation of EP2 receptors, cholera-toxin-sensitive G-proteins and cAMP-dependent protein kinase. Via this mechanism, PGE(2) may facilitate the transmission of nociceptive input through the spinal cord dorsal horn to higher brain areas where pain becomes conscious.
尽管前列腺素（PGs）在中枢神经系统对疼痛的敏化过程中发挥着关键作用，但其导致疼痛感知增强的细胞和分子靶点仍不明确。在此，我们研究了前列腺素E2（PGE2）对大鼠脊髓背角神经元快速突触传递的影响，脊髓背角是疼痛通路中突触整合的首个部位。我们确定抑制性（士的宁敏感）甘氨酸受体是PGE2的一个特定靶点。低纳摩尔浓度的PGE2可降低抑制性甘氨酸能突触传递，而前列腺素F2α（PGF2α）、前列腺素D2（PGD2）或前列腺素I2（PGI2）则无此作用，同时γ-氨基丁酸A型（GABAA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA）受体介导的传递不受影响。甘氨酸受体的抑制通过一种涉及激活EP2受体、霍乱毒素敏感的G蛋白和环磷酸腺苷（cAMP）依赖性蛋白激酶的突触后机制发生。通过这种机制，PGE2可能促进伤害性输入通过脊髓背角传递至更高的脑区，在这些脑区疼痛会变得有意识。
