Pathological activity in mediodorsal thalamus of rats with spinal cord injury pain.
Pathological activity in mediodorsal thalamus of rats with spinal cord injury pain.
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DOI：
10.1523/jneurosci.2639-12.2013
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发表时间：
2013-02-27
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影响因子：
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通讯作者：
Keller A
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文献类型：
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作者：
Whitt JL;Masri R;Pulimood NS;Keller A
脊髓损伤 (SCI) 不仅会导致运动缺陷，还会给许多患者带来难以忍受的慢性疼痛 (SCI-疼痛)。我们之前已经在啮齿动物模型中证明，SCI 会抑制 GABA 能核、未定带 (ZI) 的活性，并随之增加其主要目标之一丘脑后核 (PO) 的活性； PO 活性的增加与 SCI 后痛觉过敏的维持和表达相关。在这里，我们检验了这样的假设：SCI 会导致 ZI 调节的其他丘脑核团（特别是与疼痛的情绪情感方面有关的内侧丘脑 (MD)）出现类似的病理性增加。我们记录了麻醉或清醒大鼠 MD 的单单位和多单位活动，并将 SCI 大鼠的数据与假手术对照（麻醉实验）的数据或损伤前相同动物的数据（清醒实验）进行比较。与我们的假设一致，来自 SCI 大鼠的 MD 神经元表现出自发放电率以及对有害刺激反应的强度和持续时间显着增加。在一组麻醉动物中，通过药物灭活幼稚大鼠的 ZI 产生了类似的 MD 神经元活性变化，这表明 SCI 后 MD 的变化与 ZI 抑制的抑制有关。这些数据支持我们的假设，即 SCI 疼痛至少部分是由于与疼痛的感觉辨别和情绪情感成分相关的丘脑核团的抑制丧失所致。
Spinal cord injury (SCI) results not only in motor deficits, but produces, in many patients, excruciating chronic pain (SCI-Pain). We have previously shown, in a rodent model, that SCI causes suppression of activity in the GABAergic nucleus, zona incerta (ZI), and concomitant increased activity in one of its main targets, the posterior nucleus of the thalamus (PO); the increased PO activity is correlated with the maintenance and expression of hyperalgesia after SCI. Here, we test the hypothesis that SCI causes a similar pathological increase in other thalamic nuclei regulated by ZI, specifically the mediodorsal thalamus (MD), involved in the emotional-affective aspects of pain. We recorded single and multi-unit activity from MD of either anesthetized or awake rats, and compared data from rats with SCI with data from sham-operated controls (anesthetized experiments) or with data from the same animals pre-lesion (awake experiments). Consistent with our hypothesis, MD neurons from rats with SCI show significant increases in spontaneous firing rates, and in the magnitude and duration of responses to noxious stimuli. In a subset of anesthetized animals, similar changes in activity of MD neurons were produced by pharmacologically inactivating ZI in naïve rats, suggesting that the changes in MD after SCI are related to suppressed inhibition from ZI. These data support our hypothesis that SCI-Pain results, at least in part, from a loss of inhibition to thalamic nuclei associated with both the sensory-discriminative and emotional-affective components of pain.