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

1. 在慢性收缩神经损伤模型中，定量评估痛觉过敏和异位性痛觉变化的时间过程，证实了这一时间过程与脊髓背角gaba能抑制性中间神经元形态变化的高度相关。这些gaba能中间神经元的数量和免疫反应性在神经损伤后3天开始减少，在损伤后3周内未观察到双侧免疫反应性。损伤后约7周，对侧gaba能免疫反应性恢复至手术前水平；另一方面，在同侧，即使在手术后7周，恢复也不完全。脊髓背角退行性神经元（暗神经元）变化的时间过程与上述变化相似。在脊髓损伤模型中，观察脊髓浅背角gaba能和甘氨酸能抑制性中间神经元变化的时间过程。术后3天观察到双侧GABA免疫反应性轻微下降。双侧GABA免疫反应性下降在术后1周加速，并持续至少3周，此时GABA能免疫反应成分开始恢复。神经损伤后1周甘氨酸能纤维和神经末梢减少，时间变化过程与此相似。皂苷是神经营养因子之一，在神经性疼痛模型中被证明能有效缓解某些疼痛行为。为了评估各种神经营养因子的作用，采用CCI模型进行肾上腺髓质移植。肾上腺髓质移植对脊髓背角易损抑制性中间神经元的治疗作用得到证实，行为性痛觉过敏和异常性痛觉明显加速恢复。

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.