Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain
Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain
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DOI：
10.1016/s0304-3959(03)00011-3
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发表时间：
2003-07-01
期刊：
影响因子：
7.4
通讯作者：
Todd, AJ
中科院分区：
文献类型：
--
作者：
Polgár, E;Hughes, DI;Todd, AJ
GABA 和甘氨酸是脊髓背角许多神经元使用的抑制性神经递质，鞘内注射 GABA(A) 和甘氨酸受体拮抗剂会产生异常性疼痛的行为症状，表明这些递质在脊髓疼痛机制中具有重要作用。几项研究描述了神经损伤模型中背角 GABA 免疫反应性神经元的大量损失，有人认为这可能与抑制作用的丧失有关，从而导致神经性疼痛的行为体征。我们对慢性缩窄神经结扎后 2 周显示 GABA 和/或甘氨酸免疫反应性的大鼠背角 I、II 和 III 层神经元的比例进行了定量体视学分析损伤（CCI）模型，以及假手术和幼稚动物。此时，接受 CCI 的大鼠表现出同侧后爪对辐射热刺激的缩回潜伏期显着缩短，表明热痛觉过敏已经发生。然而，与这些动物的对侧相比，我们没有观察到同侧背角 I-III 层中显示 GABA 或甘氨酸免疫反应性的神经元比例有任何变化，并且这些比例与假手术或首次实验动物中观察到的比例没有显着差异。此外，我们没有发现任何证据表明经历 CCI 的动物 I-III 层神经毡中 GABA 或甘氨酸免疫染色发生变化。我们的结果表明，GABA 能或甘氨酸能神经元的显着损失对于 CCI 神经性疼痛模型中热痛觉过敏的发生并不是必需的。 (C) 2003 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
GABA and glycine are inhibitory neurotransmitters used by many neurons in the spinal dorsal horn, and intrathecal administration of GABA(A) and glycine receptor antagonists produces behavioural signs of allodynia, suggesting that these transmitters have an important role in spinal pain mechanisms. Several studies have described a substantial loss of GABA-immunoreactive neurons from the dorsal horn in nerve injury models, and it has been suggested that this may be associated with a loss of inhibition, which contributes to the behavioural signs of neuropathic pain.We have carried out a quantitative stereological analysis of the proportions of neurons in laminae I, II and III of the rat dorsal horn that show GABA- and/or glycine-immunoreactivity 2 weeks after nerve ligation in the chronic constriction injury (CCI) model, as well as in sham-operated and naive animals. At this time, rats that had undergone CCI showed a significant reduction in the latency of withdrawal of the ipsilateral hindpaw to a radiant heat stimulus, suggesting that thermal hyperalgesia had developed. However, we did not observe any change in the proportion of neurons in laminae I-III of the ipsilateral dorsal horn that showed GABA- or glycine-immunoreactivity compared to the contralateral side in these animals, and these proportions did not differ significantly from those seen in sham-operated or naive animals. In addition, we did not see any evidence for alterations of GABA- or glycine-immunostaining in the neuropil of laminae I-III in the animals that had undergone CCI.Our results suggest that significant loss of GABAergic or glycinergic neurons is not necessary for the development of thermal hyperalgesia in the CCI model of neuropathic pain. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.