Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons
Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons
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DOI：
10.1016/j.pain.2010.09.008
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发表时间：
2010-12-01
期刊：
影响因子：
7.4
通讯作者：
Cervero, Fernando
中科院分区：
文献类型：
--
作者：
Pitcher, Mark H.;Cervero, Fernando
Na（+），K（+），2Cl（-）协同转运蛋白1（NKCC 1）在炎症刺激相关的痛觉过敏中起着关键作用。NKCC 1有助于维持背根神经节（DRG）神经元中的高[Cl（-）]（i），当GABA（A）受体被激活时，背根神经节（DRG）神经元引起初级传入去极化（PAD）。增强GABA诱导的去极化，通过增加NKCC 1活性，已被假设产生足够强度的顺向尖峰活动，以解释触摸诱导的疼痛。在本研究中，我们研究了这一假设，在体内电生理学对大鼠背角神经元的脊髓阻滞NKCC 1足底辣椒素诱导的背角神经元敏化的影响进行了检查。用玻璃微电极记录麻醉大鼠脊髓背角单个宽动态范围（WDR）和伤害性特异性（NS）神经元活动。背角神经元的感受野的足底表面的后爪进行了研究。在足底注射0.3ml 0.1%辣椒素（CAP）前10分钟、CAP后40分钟和在脊髓上局部应用NKCC 1阻断剂布美他尼（BTD; 500 μ M）后15分钟记录对机械刺激（刷子、von Frey细丝）的神经元反应。CAP后，低和高阈值刺激的皮肤感受野产生了显着的增强尖峰频率比前CAP值在WDR和NS神经元。脊髓BTD应用将尖峰频率降低至基线水平，并减弱CAP诱导的背景活动增加。我们的数据支持这一假设，NKCC 1起着重要的作用，在敏化背角神经元后，外周炎症损伤。(C)2010年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The Na(+), K(+), 2Cl(-) co-transporter type 1 (NKCC1) plays a pivotal role in hyperalgesia associated with inflammatory stimuli. NKCC1 contributes to maintain high [Cl(-)](i) in dorsal root ganglia (DRG) neurons which cause primary afferent depolarization (PAD) when GABA(A) receptors are activated. Enhanced GABA-induced depolarization, through increased NKCC1 activity, has been hypothesized to produce orthodromic spike activity of sufficient intensity to account for touch-induced pain. In the present study, we investigate this hypothesis using in vivo electrophysiology on rat dorsal horn neurons; the effects of spinal blockade of NKCC1 on intraplantar capsaicin-induced sensitization of dorsal horn neurons were examined. Single wide dynamic range (WDR) and nociceptive specific (NS) neuron activity in the dorsal horn was recorded using glass microelectrodes in anesthetized rats. Dorsal horn neurons with a receptive field on the plantar surface of the hindpaw were studied. Neuronal responses to mechanical stimuli (brush, von Frey filaments) were recorded ten minutes before intraplantar injection of 0.3 ml 0.1% capsaicin (CAP), 40 min after CAP and 15 min after local application of the NKCC1 blocker bumetanide (BTD; 500 mu M) on the spinal cord. After CAP, low and high threshold stimulation of the cutaneous receptive field produced a significant enhancement in spike frequency over pre-CAP values in both WDR and NS neurons. Spinal BTD application reduced the spike frequency to baseline levels as well as attenuated the CAP-induced increases in background activity. Our data support the hypothesis that NKCC1 plays an important role in the sensitization of dorsal horn neurons following a peripheral inflammatory insult. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.