Yan Lai-Hong, Hou Jun-Feng, Liu Ming-Gang, Li Meng-Meng, Cui Xiu-Yu, Lu Zhuo-Min, Zhang Fu-Kang, An Yang-Yuan, Shi Lin, Chen Jun
Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, PR China.
Pharmacol Res. 2009 May;59(5):290-9. doi: 10.1016/j.phrs.2009.01.012. Epub 2009 Feb 5.
Although the postsynaptic events responsible for development of pathological pain have been intensively studied, the relative contribution of presynaptic neurotransmitters to the whole process remains less elucidated. In the present investigation, we sought to measure temporal changes in spinal release of both excitatory amino acids (EAAs, glutamate and aspartate) and inhibitory amino acids (IAAs, glycine, ?-aminobutyric acid and taurine) in response to peripheral inflammatory pain state. The results showed that following peripheral chemical insult induced by subcutaneous bee venom (BV) injection, there was an initial, parallel increase in spinal release of both EAAs and IAAs, however, the balance between them was gradually disrupted when pain persisted longer, with EAAs remaining at higher level but IAAs at a level below the baseline. Moreover, the EAAs-IAAs imbalance at the spinal level was dependent upon the ongoing activity from the peripheral injury site. Intrathecal blockade of ionotropic (NMDA and non-NMDA) and metabotropic (mGluRI, II, III) glutamate receptors, respectively, resulted in a differential inhibition of BV-induced different types of pain (persistent nociception vs. hyperalgesia, or thermal vs. mechanical hyperalgesia), implicating that spinal antagonism of any specific glutamate receptor subtype fails to block all types of pain-related behaviors. This result provides a new line of evidence emphasizing an importance of restoration of EAAs-IAAs balance at the spinal level to prevent persistence or chronicity of pain.
尽管对导致病理性疼痛发展的突触后事件已进行了深入研究，但突触前神经递质在整个过程中的相对作用仍不太清楚。在本研究中，我们试图测量脊髓中兴奋性氨基酸（EAA，谷氨酸和天冬氨酸）和抑制性氨基酸（IAA，甘氨酸、γ-氨基丁酸和牛磺酸）释放的时间变化，以应对外周炎症性疼痛状态。结果表明，皮下注射蜂毒（BV）诱导外周化学损伤后，EAA和IAA在脊髓中的释放最初同时增加，然而，当疼痛持续时间更长时，它们之间的平衡逐渐被打破，EAA保持在较高水平，而IAA则低于基线水平。此外，脊髓水平的EAA-IAA失衡取决于外周损伤部位的持续活动。分别鞘内阻断离子型（NMDA和非NMDA）和代谢型（mGluRI、II、III）谷氨酸受体，导致对BV诱导的不同类型疼痛（持续性伤害感受与痛觉过敏，或热痛觉过敏与机械性痛觉过敏）的不同抑制作用，这表明脊髓中任何特定谷氨酸受体亚型的拮抗作用都不能阻断所有类型的疼痛相关行为。这一结果提供了新的证据，强调恢复脊髓水平的EAA-IAA平衡对预防疼痛持续或慢性化的重要性。
