Dougherty P M, Palecek J, Zorn S, Willis W D
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-0843.
Brain Res Brain Res Rev. 1993 May-Aug;18(2):227-46. doi: 10.1016/0165-0173(93)90003-i.
Sensitization of dorsal horn neurons following injury may underlie the generation of secondary hyperalgesia and so the chemical basis of sensitization is now receiving considerable attention. The present study used microiontophoretic applications of excitatory amino acids (EAA's) and substance P (SP) to test their roles in the sensitization of primate spinothalamic tract (STT) neurons. Of 70 STT cells examined in laminae I-VI of the dorsal horn, 40 showed an increase in responses to one or more EAA's following their co-application with SP. The increased responses were usually specific to either N-methyl-D-aspartate (NMDA) or to the non-NMDA agonists, quisqualate (QUIS) or D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA). The enhancement of EAA responses was long-lasting (> 15 min) in 18 cases, was accompanied by similarly long-lasting increases in responses to mechanical stimulation of the receptive field in 14 cases and was accompanied by an increase in responses to either glutamate (Glu) or aspartate (Asp) in eleven cases. A global decrease in all EAA responses tested was produced in 26 other STT neurons. The inhibition, unlike the increases, was generalized to both NMDA and non-NMDA ligands, was long-lasting in only six cases and was never accompanied by a change in the responses to mechanical stimuli. The excitatory and inhibitory effects of SP on the responses to NMDA were uniformly reversed by the NK-1 receptor selective antagonist, CP96345. In contrast, only the inhibitory effects of SP on the responses to QUIS or AMPA were reversed by CP96345. The long-lasting enhancement of EAA responses by SP may follow the combined synaptic release of the natural ligands in vivo, resulting in the sensitization of dorsal horn neurons and secondary hyperalgesia. However, the reductions in EAA responses produced by SP are problematic for this hypothesis and need further elucidation.
损伤后背角神经元的敏化可能是继发性痛觉过敏产生的基础，因此敏化的化学基础目前受到了相当多的关注。本研究采用微离子电泳法施加兴奋性氨基酸（EAA）和P物质（SP），以测试它们在灵长类动物脊髓丘脑束（STT）神经元敏化中的作用。在背角I-VI层检查的70个STT细胞中，40个在与SP共同施加后对一种或多种EAA的反应增强。增强的反应通常对N-甲基-D-天冬氨酸（NMDA）或非NMDA激动剂喹氨酸（QUIS）或D，L-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）具有特异性。在18例中，EAA反应的增强持续时间较长（>15分钟），在14例中，对感受野机械刺激的反应同样出现了持续时间较长的增加，在11例中，对谷氨酸（Glu）或天冬氨酸（Asp）的反应增加。在另外26个STT神经元中，所有测试的EAA反应出现了整体下降。与增加不同，这种抑制作用对NMDA和非NMDA配体都有普遍影响，仅在6例中持续时间较长，并且从未伴随着对机械刺激反应的改变。SP对NMDA反应的兴奋和抑制作用均被NK-1受体选择性拮抗剂CP96345完全逆转。相比之下，CP96345仅逆转了SP对QUIS或AMPA反应的抑制作用。SP对EAA反应的长期增强可能是体内天然配体联合突触释放的结果，导致背角神经元敏化和继发性痛觉过敏。然而，SP引起的EAA反应降低对于这一假设来说存在问题，需要进一步阐明。
