Sorkin Linda S, Puig Sylvie, Jones Denise L
Anesthesiology Research Laboratory, University of California, San Diego, CA, USA.
Pain. 1998 Aug;77(2):181-190. doi: 10.1016/S0304-3959(98)00094-3.
In this study, we sought to characterize the effects of focal GABA(A) receptor antagonism on spontaneous and evoked activity in dorsal horn neurons of the alpha-chloralose anesthetized cat. Bicuculline (0.5, 1.0 mM) applied near the neurons through a transparenchymal dialysis fiber resulted in increased evoked activity in nociceptive dorsal horn neurons. Hair deflection was the stimulus most affected, followed by both low and high threshold tonic mechanical stimulation of the receptive field. In addition, neurons displayed increased background discharge and a subpopulation developed an increased afterdischarge to noxious mechanical stimulation. This is in contrast to our previous work with glycine receptor antagonism where only the evoked response to hair follicle activation was significantly enhanced. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) was without any apparent effect on either basal or bicuculline-enhanced responses. Co-administration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1.0 mM) with the bicuculline non-selectively blocked both low and high threshold mechanical input. The inability of AP-7 to reverse the bicuculline-associated hyperreactivity also contrasts with the AP-7 reversal of the strychnine-associated hyperreactivity. These results point out that, while GABA and glycine are frequently co-localized in cells of the spinal dorsal horn and both appear to mediate tonic inhibitory control systems, they are not at all equivalent and are subject to different modulatory pharmacologies. Removal of each influence may model a different component of neuropathic pain.
在本研究中，我们试图描述局灶性γ-氨基丁酸A（GABA(A)）受体拮抗作用对α-氯醛糖麻醉猫背角神经元自发活动和诱发活动的影响。通过透明质透析纤维在神经元附近施加荷包牡丹碱（0.5、1.0 mM）导致伤害性背角神经元的诱发活动增加。毛发偏转是受影响最大的刺激，其次是感受野的低阈值和高阈值强直机械刺激。此外，神经元的背景放电增加，并且有一个亚群对有害机械刺激的后放电增加。这与我们之前使用甘氨酸受体拮抗作用的研究形成对比，在之前的研究中，只有对毛囊激活的诱发反应显著增强。随后共同施用N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（AP-7，2.0 mM）对基础反应或荷包牡丹碱增强的反应均无明显影响。将非NMDA兴奋性氨基酸受体拮抗剂（CNQX，1.0 mM）与荷包牡丹碱共同施用可非选择性地阻断低阈值和高阈值机械输入。AP-7无法逆转与荷包牡丹碱相关的反应过度，这也与AP-7逆转与士的宁相关的反应过度形成对比。这些结果指出，虽然GABA和甘氨酸经常共定位于脊髓背角细胞中，并且两者似乎都介导紧张性抑制控制系统，但它们完全不等同，并且受到不同的调节药理学影响。去除每种影响可能模拟神经性疼痛的不同组成部分。
