Elucidation of Intracellular Signal Transduction Pathway Involved in the Processing of Nociceptive Information -- Focusing on the Role of Neurotrophic Factor --

1.在慢性压迫性神经损伤模型中，定量评估了痛觉过敏和异常性疼痛变化的时间过程，并证明了该时间过程与脊髓背角GABA能抑制性中间神经元的形态学变化之间的高度相关性。损伤后第3天，同侧GABA能中间神经元的数量和免疫反应性开始减少，损伤后3周左右两侧均未见GABA能中间神经元的免疫反应性。在对侧，GABA能免疫反应性在损伤后约7周恢复至术前水平;另一方面，在同侧，即使在术后7周恢复也不完全。脊髓背角变性神经元（Dark神经元）的变化与上述变化的时程相似.在脊神经损伤模型中，观察脊髓背角浅层GABA能和甘氨酸能抑制性中间神经元的变化。术后3天，观察到双侧GABA免疫反应性略有下降。双侧GABA免疫反应性的减少在术后1周加速，并持续至少3周，此时GABA能免疫反应性成分开始恢复。神经损伤后1周，甘氨酸能纤维和终末减少，其变化的时间过程与损伤前相似. saposin是神经营养因子之一，在神经病理性疼痛模型中被证明能有效地减轻某些疼痛行为.为了评价各种神经营养因子的作用，使用CCI模型进行肾上腺髓质移植。肾上腺髓质移植对脊髓背角内脆弱的抑制性中间神经元有明显的治疗作用，并能促进行为性痛敏和异常性痛的恢复。

1. In the chronic constriction nerve injury model, the time course of changes in hyperalgesia and allodynia were quantitatively assessed and the high correlation between this time course and that of morphological changes in GABAergic inhibitory interneurons in the spinal dorsal horn was proved. The number and immunoreactivity of these GABAergic interneurons begin to decrease ipsiaterally at 3 days following nerve injury and no immunoreactivity could be observed bilaterally during the 3 weeks following injury. In the contralateral side, GABAergic immunoreactivity recovered approximately to the presurgical level at about 7 weeks after injury ; on the other hand in the ipsilateral side the recovery was incomplete even at 7 weeks following surgery. The time course of changes in the degenerated neurons in the spinal dorsal horn (Dark neurons) was similar to that of these changes.2. In the spinal nerve injury model, the time course of changes in GABAergic and glycinergic inhibitory interneurons in the superficial dorsal horn of the spinal cord were observed. A slight decrease in GABA immunoreactivity was observed bilaterally 3 days following surgery. Bilateral decrease in GABA immunoreactivity was accelerated at I week and continued for at least 3 weeks after surgery, when GABAergic immunoreactive components began to recover. Glycinergic fibers and terminals diminished 1 week ater nerve injury and the time course of the changes followed a similar course.3. One of the neurotrophic factors, saposin was proved to be effective in the alleviation of some pain behavior in neuropathic pain models.4. In order to evaluate the effect of various neurotrophic factors, adrenal medurally transplantation was performed using the CCI model. The therapeutic effect of adrenal medullary transplants on the vulnerable inhibitory interneurons in the spinal dorsal horn was proved and acceralated recovery of behavioral hyperalgesia and allodynia was evident.