Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
J Neurophysiol. 2010 Jun;103(6):3044-53. doi: 10.1152/jn.01070.2009. Epub 2010 Mar 31.
Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.
中枢性疼痛综合征（CPS）是一种使人虚弱的病症，影响了大量的中枢神经系统原发性损伤或功能障碍的患者，最常见的原因是脊髓损伤、中风和多发性硬化症损伤。CPS 发展和维持的病理生理过程知之甚少。我们最近在 CPS 的动物模型中表明，后丘脑核（PO）中的神经元自发活动和诱发活动增加。我们还证明，这些变化是由于来自未定带（ZI）的抑制性输入被抑制所致。前脑桥核（APT）是一个间脑核，投射到 PO 和 ZI，这表明它可能参与 CPS 的病理生理学。在这里，我们通过记录脊髓损伤引起 CPS 的麻醉大鼠 APT 中的单个单位来测试 APT 活动异常与 CPS 相关的假设。与假手术对照组相比，脊髓损伤动物的 APT 神经元放电率增加。这种增加是由于投射到并抑制 ZI 的紧张型神经元的放电选择性增加，以及快速爆发和缓慢节律神经元的爆发增加。我们还表明，在正常动物中，抑制 APT 会导致 PO 中一部分神经元的自发性活动和诱发反应增加。综上所述，这些发现表明 APT 调节 PO 对 ZI 的输入，而 CPS 期间增强的 APT 活性有助于 CPS 中 PO 神经元的异常高活性。
