Chen Shao-Rui, Pan Hui-Lin
Department of Anesthesiology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
J Pharmacol Exp Ther. 2005 Jan;312(1):120-6. doi: 10.1124/jpet.104.073817. Epub 2004 Sep 16.
Increased glutamatergic input to spinal dorsal horn neurons constitutes an important mechanism for neuropathic pain. However, the role of group III metabotropic glutamate receptors (mGluRs) in regulation of nociception and dorsal horn neurons in normal and neuropathic pain conditions is not fully known. In this study, we determined the effect of the group III mGluR specific agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) on nociception and dorsal horn projection neurons in normal rats and a rat model of neuropathic pain. Tactile allodynia was induced by ligation of L5/L6 left spinal nerves in rats. Allodynia was determined by von Frey filaments in nerve-injured rats. The nociceptive threshold was tested using a radiant heat and a Randall-Selitto pressure device in normal rats. Single-unit activity of ascending dorsal horn neurons was recorded from the lumbar spinal cord in anesthetized rats. An intrathecal (5-30 microg) L-AP4 dose-dependently attenuated allodynia in nerve-injured rats but had no antinociceptive effect in normal rats. Topical spinal application of 5 to 50 microM L-AP4 also significantly inhibited the evoked responses of ascending dorsal horn neurons in nerve-ligated but not normal rats. Furthermore, blockade of spinal group III mGluRs significantly decreased the withdrawal threshold and increased the evoked responses of dorsal horn neurons in normal but not nerve-injured rats. These data suggest that group III mGluRs play distinct roles in regulation of nociception and dorsal horn neurons in normal and neuropathic pain states. Activation of spinal group III mGluRs suppresses allodynia and inhibits the hypersensitivity of dorsal horn projection neurons associated with neuropathic pain.
脊髓背角神经元的谷氨酸能输入增加是神经性疼痛的重要机制。然而，III组代谢型谷氨酸受体（mGluRs）在正常和神经性疼痛状态下对伤害感受和背角神经元的调节作用尚不完全清楚。在本研究中，我们确定了III组mGluR特异性激动剂L(+)-2-氨基-4-磷酸丁酸（L-AP4）对正常大鼠和神经性疼痛大鼠模型的伤害感受及背角投射神经元的影响。通过结扎大鼠左侧L5/L6脊神经诱导触觉异常性疼痛。用von Frey细丝测定神经损伤大鼠的异常性疼痛。用辐射热和Randall-Selitto压力装置测试正常大鼠的伤害性阈值。在麻醉大鼠的腰脊髓记录背角神经元的单单位活动。鞘内注射（5 - 30微克）L-AP4剂量依赖性地减轻神经损伤大鼠的异常性疼痛，但对正常大鼠无抗伤害感受作用。局部脊髓应用5至50微摩尔/升的L-AP4也显著抑制神经结扎大鼠而非正常大鼠背角神经元的诱发性反应。此外，阻断脊髓III组mGluRs显著降低正常大鼠而非神经损伤大鼠的撤腿阈值并增加背角神经元的诱发性反应。这些数据表明，III组mGluRs在正常和神经性疼痛状态下对伤害感受和背角神经元的调节中发挥不同作用。激活脊髓III组mGluRs可抑制异常性疼痛并抑制与神经性疼痛相关的背角投射神经元的超敏反应。
