Zeilhofer H U
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054 Erlangen(Germany).
Cell Mol Life Sci. 2005 Sep;62(18):2027-35. doi: 10.1007/s00018-005-5107-2.
Alterations in synaptic transmission within the spinal cord dorsal horn play a key role in the development of pathological pain. While N-methyl-D-aspartate (NMDA) receptors and activity-dependent synaptic plasticity have been the focus of research for many years, recent evidence attributes very specific functions to inhibitory glycinergic and gamma-aminobutyric acid (GABA)-ergic neurotransmission in the generation of inflammatory and neuropathic pain. The central component of inflammatory pain originates from a disinhibition of dorsal horn neurons, which are relieved from glycinergic neurotransmission by the inflammatory mediator prostaglandin E2 (PGE2). PGE2 activates prostaglandin E receptors of the EP2 subtype and leads to a protein kinase A-dependent phosphorylation and inhibition of glycine receptors containing the alpha3 subunit (GlyRalpha3). This GlyRalpha3 is distinctly expressed in the superficial dorsal horn, where nociceptive afferents terminate. Other but probably very similar disinhibitory mechanisms may well contribute to abnormal pain occurring after peripheral nerve injury.
脊髓背角内突触传递的改变在病理性疼痛的发展中起关键作用。虽然N-甲基-D-天冬氨酸（NMDA）受体和活动依赖性突触可塑性多年来一直是研究的重点，但最近的证据表明，抑制性甘氨酸能和γ-氨基丁酸（GABA）能神经传递在炎症性和神经性疼痛的产生中具有非常特定的功能。炎症性疼痛的核心成分源于背角神经元的去抑制，炎症介质前列腺素E2（PGE2）解除了甘氨酸能神经传递对其的抑制作用。PGE2激活EP2亚型的前列腺素E受体，并导致蛋白激酶A依赖性磷酸化以及对含有α3亚基的甘氨酸受体（GlyRα3）的抑制。这种GlyRα3在浅表背角中特异性表达，伤害性传入神经在此处终止。其他但可能非常相似的去抑制机制很可能导致周围神经损伤后出现的异常疼痛。
