Neuronal/Synaptic Reorganization after Partial Deafferentation

该项目分别涉及外周神经收缩性损伤或脊髓丘脑束神经元或其投射的特定病变导致部分传入阻滞后，脊髓和体感丘脑浅层背角的神经元和突触组织的可塑性。我们已经在大鼠中表明，作为人类神经损伤模型的坐骨神经损伤在神经损伤后的前3至21天内导致背角抑制回路的深刻改变，并且这些回路的变化与动物的疼痛行为直接相关。我们现在希望检查在神经损伤后存活数月的类似动物。人类经常有神经损伤，导致数月或数年的主要疼痛综合征，我们希望确定神经损伤的大鼠最终是否恢复，以及我们是否可以确定恢复的神经基础。糖尿病神经基础恢复模型的平行研究。将与J. Levine的实验室进行糖尿病神经病变（人类疼痛和残疾的常见原因）模型的平行研究，其中我们将检查表现出痛觉过敏的糖尿病大鼠的隐神经和脊髓，因为对糖尿病神经病变中传入通路可能发生的变化知之甚少。在与HL Fields的合作研究中，我们将确定脊髓丘脑束神经元的特定病变是否会导致大鼠体感丘脑的重组。然后，我们将扩展这些研究，以检查大鼠和猴子丘脑核团组织中可能的传入神经阻滞诱导的变化，这些变化投射到扣带皮层，扣带皮层被认为是动物和人类疼痛的情绪和厌恶行为的情感基础的重要区域。我们相信我们的研究与人类疼痛综合征直接相关，结果表明躯体感觉系统神经元回路的可塑性变化可能在疼痛的发生和维持中发挥重要作用。在导致参与疼痛感知和反应的主要脊髓和前脑中枢部分传入神经阻滞的损伤患者中，对神经系统变化的理解是设计治疗人类疼痛综合征的疗法的重要步骤。

Project concerns the plasticity of the neuronal and synaptic organization of the superficial dorsal horn of the spinal cord and of the somatosensory thalamus following partial deafferentation by constriction injury of peripheral nerve or specific lesions of spinothalamic tract neurons or their projects, respectively. We have already shown in the rat that sciatic nerve lesions that are models of human nerve injury result in profound alterations in the inhibitory circuitry of the dorsal horn in the first 3 to 21 days following nerve lesions, and that these changes in circuitry are directly correlated with pain behavior in the animals. We now wish to examine similar animals that survive for many months following nerve injury. Humans often have nerve injuries that result in major pain syndromes for many months and years, and we wish to determine whether rats with nerve injury eventually recover and whether we can identify the neural basis for the recovery. A parallel study of a model of diabetic neural basis for the recovery. A parallel study of a model of diabetic neuropathy, a common cause of pain and disability in humans, will be carried out with the laboratory of J. Levine, in which we will examine the saphenous nerve and the spinal cord in diabetic rats that exhibit hyperalgesia, as little is known about the possible changes that might occur in afferent pathways in diabetic neuropathy. In a collaborative study with HL Fields, we will determine whether specific lesions of spinothalamic tract neurons will result in the reorganization of the rat somatosensory thalamus. We will then extend these studies to examine possible deafferentation-induced changes in the organization of the thalamic nuclei in rat and monkey that project to the cingulate cortex, a region considered to be important in the emotional basis of emotional and aversive behavior in animals and humans with pain. We believe that our studies have a direct relevance to human pain syndromes and the results indicate that plastic changes in the neuronal circuitry of the somatosensory system may play a substantial role in the genesis and maintenance of pain. In people with injuries that result in partial deafferentation of major spinal cord and forebrain centers involved in the perception of, and the response to, pain, an understanding of nervous system changes is an important step in the design of therapies to treat human pain syndromes.