Maladaptive plasticity following spinal cord injury

对大脑和脊髓的侮辱不仅会导致运动、感觉和 不仅是认知缺陷，而且还有慢性、痛苦和无情的疼痛，在很大程度上抵抗治疗。在大多数患者中，疼痛在最初的侮辱后几周或几个月开始，包括因伤害性刺激而增加的疼痛(痛觉过敏)，对先前无害的刺激产生的疼痛(超敏)，以及自发疼痛。脊髓 皮损通常会产生特别痛苦的CPS症状，伴随着持续的疼痛 可以是弥漫性的，双侧的，并可能延伸到“病变下方”，到脊柱损伤的尾部。CPS的延迟表达和疼痛症状的弥漫性定位表明，病理生理学不仅反映了对失神经脊椎节段的直接影响。相反，CPS的这些特征强烈地表明 来自身体不同部位输入的脊柱上结构的非适应性可塑性 这个应用程序的最终目标是找出因果关系 对脊髓损伤后的这种不适应可塑性负责。 为此，我们采用了一种啮齿动物脊髓损伤模型。我们证明了这一点 患有CPS的大鼠后核神经元活性异常高 丘脑(PO)。我们还证明，PO和相关丘脑核团的活动受到来自未定带和前额叶的抑制性输入的严格调控。 顶盖前核。这些发现表明CPS与适应不良有关。 中枢-丘脑通路的可塑性。基于这些令人振奋的新发现，我们 提出CPS可能是由于丘脑带对丘脑核团的抑制所致 Incerta和顶盖前前核。拟议的研究将使用电生理学、行为学和解剖学方法来测试从我们的总体假设中出现的4个关键预测的有效性。

Insults to the brain and spinal cord result not only in debilitating motor, sensory and cognitive deficits, but also in chronic, excruciating and relentless pain that is largely resistant to treatment. In most patients, pain starts weeks or months after the original insult, and includes increased pain with noxious stimulation (hyperalgesia), pain in response to previously innocuous stimuli (allodynia), and spontaneous pain. Spinal cord lesions typically produce particularly painful CPS symptoms, with unremitting pain that can be diffuse, bilateral, and may extend, "below-lesion", to locations caudal to the spinal injury. The delayed expression of CPS and the diffuse localization of painful symptoms suggest that the pathophysiology does not reflect only direct effects at the denervated spinal segments. Rather, these features of CPS strongly suggest the occurence of maladaptive plasticity in supraspinal structures at which inputs from various body parts converge, 'The ultimate goal of this application is to identify the factors that are causally responsible for this maladaptive plasticity following spinal cord injury. To this end, we adapted a rodent spinal cord injury model of CPS. We demonstrated that rats suffering from CPS have abnormally high neuronal activity in the posterior nucleus of the thalamus (PO). We also demonstrated that the activity of PO, and related thalamic nuclei, is tightly regulated by inhibitory inputs from the zona incerta and the anterior pretectal .nucleus. These findings suggest that CPS is associated with maladaptive plasticity in the incerto-thalamic pathway. Based on these exciting new findings, we propose that CPS can result from suppressed inhibition to thalamic.nuclei from zona incerta and the anterior pretectal nucleus. The proposed studies will use electrophysiological, behavioral and anatomical approached to test the validity of 4 key predictions that emerge from our overarching hypothesis.