Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex
Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex
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DOI：
10.1038/nature01808
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发表时间：
2003-07-17
期刊：
影响因子：
64.8
通讯作者：
Ohara, PT
中科院分区：
文献类型：
--
作者：
Jasmin, L;Rabkin, SD;Ohara, PT
众所周知，疼痛感知可以通过情绪、注意力和认知，或通过直接刺激大脑皮层来改变（1），但我们对疼痛皮层调制的神经机制知之甚少。疼痛刺激持续激活的少数皮质区域之一是吻侧无颗粒岛叶皮质（RAIC），与皮质的其他部分一样，神经递质γ-氨基丁酸（GABA）强烈抑制神经元活动。在这里，我们表明，在RAIC的GABA神经传递的变化可以提高或降低疼痛阈值产生镇痛或痛觉过敏，分别在自由活动的大鼠。通过使用酶抑制剂或由病毒载体介导的基因转移，局部增加GABA，通过增强脊髓伤害性神经元的下行抑制产生持久的镇痛作用。选择性激活携带GABA（B）受体的RAIC神经元通过投射到杏仁核（一个涉及疼痛和恐惧的区域）产生痛觉过敏。虽然大多数研究都集中在大脑皮层作为伤害性处理的终点的作用，我们认为，大脑皮层活动可以改变痛阈的设定点，在一个自上而下的方式。
It is known that pain perception can be altered by mood, attention and cognition, or by direct stimulation of the cerebral cortex(1), but we know little of the neural mechanisms underlying the cortical modulation of pain. One of the few cortical areas consistently activated by painful stimuli is the rostral agranular insular cortex (RAIC) where, as in other parts of the cortex, the neurotransmitter gamma-aminobutyric acid (GABA) robustly inhibits neuronal activity. Here we show that changes in GABA neurotransmission in the RAIC can raise or lower the pain threshold-producing analgesia or hyperalgesia, respectively-in freely moving rats. Locally increasing GABA, by using an enzyme inhibitor or gene transfer mediated by a viral vector, produces lasting analgesia by enhancing the descending inhibition of spinal nociceptive neurons. Selectively activating GABA(B)-receptor-bearing RAIC neurons produces hyperalgesia through projections to the amygdala, an area involved in pain and fear. Whereas most studies focus on the role of the cerebral cortex as the end point of nociceptive processing, we suggest that cerebral cortex activity can change the set-point of pain threshold in a top-down manner.