Activation of spinal GABA receptors attenuates chronic central neuropathic pain after spinal cord injury
Activation of spinal GABA receptors attenuates chronic central neuropathic pain after spinal cord injury
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DOI：
10.1089/neu.2006.23.1111
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发表时间：
2006-07-01
影响因子：
4.2
通讯作者：
Leem, Joong Woo
中科院分区：
文献类型：
--
作者：
Gwak, Young Seob;Tan, Huai Yu;Leem, Joong Woo
在这项研究中，我们研究了脊髓gaba能系统在大鼠T13脊髓半横切引起的脊髓损伤（SCI）后中枢神经性疼痛样结果中的作用。脊髓损伤后，大鼠双后爪出现机械异常性疼痛，持续时间超过40天，这可以从弱von Frey纤维引起的足爪退缩频率增加中得到证明。在幼稚大鼠中，脊髓鞘内注射GABA(A)和GABA(B)受体拮抗剂双库兰（1-5 μ g）和苯氯芬（0.1-5 μ g）分别导致机械异常性痛强度的剂量依赖性增加。脊髓内分别给予GABA(A)或GABA(B)受体激动剂muscimol （1 μ g）或巴氯芬（0.5 μ g），可减轻sci诱导的双后爪机械性异常痛。电生理实验显示，脊髓损伤大鼠腰椎背角宽动态范围（WDR）神经元在自然刺激下双侧高兴奋性增加。局部应用muscimol （1 μ g）或巴氯芬（0.5 μ g）在腰椎表面可降低sci诱导的WDR神经元反应性增高。与对照组相比，肌西莫和巴氯芬对脊髓损伤后WDR神经元行为性机械异常性痛和高兴奋性的抑制作用分别被双库兰（10 μ g）和苯氯芬（5 μ g）预处理所拮抗。本研究为脊髓抑制性张力丧失(由GABA（A)和GABA(B)受体激活介导）在脊髓损伤后中枢神经性疼痛发展中的重要作用提供了行为学和电生理学证据。
In this study, we investigated the role of the spinal GABAergic system in central neuropathic pain-like outcomes following spinal cord injury (SCI) produced by a spinal hemitransection at T13 of the rat. After SCI, mechanical allodynia develops bilaterally in both hind paws of the rat, lasting longer than 40 days, as evidenced by an increase in paw withdrawal frequency in response to a weak von Frey filament. In naive rats, intrathecal (i.t.) administration in the lumbar spinal cord of GABA(A) and GABA(B) receptor antagonists, bicuculline (1-5 mu g) and phaclofen (0.1-5 mu g), respectively, causes a dose-dependent increase in the magnitude of mechanical allodynia. The SCI-induced mechanical allodynia in both hind-paws is attenuated by i.t. administration in the lumbar spinal cord of GABA(A) or GABA(B) receptor agonists, muscimol (1 mu g) or baclofen (0.5 mu g), respectively. In electrophysiological experiments, rats with SCI show a bilateral increase in hyperexcitability in response to natural stimuli in wide dynamic range (WDR) neurons in the lumbar spinal dorsal horn. The topical application of muscimol (1 mu g) or baclofen (0.5 mu g) onto the lumbar cord surface reduce the SCI-induced increased responsiveness of WDR neurons. Inhibitory effects of muscimol and baclofen on both the behavioral mechanical allodynia and the hyperexcitability in WDR neuron with SCI compared to controls, were antagonized by pre-treatment of bicuculline (10 mu g) and phaclofen (5 mu g), respectively. This study provides behavioral and electrophysiological evidence for the important role of the loss of spinal inhibitory tone, mediated by activation of both GABA(A) and GABA(B) receptors, in the development of central neuropathic pain following SCI.