The role of cell adhesion molecules and neurotrophic factors in reconstruction of nociceptive pathways in spinal cord and brainstem after peripheralaxotomy

本研究的最终目的是了解主要感觉通路的可塑性，特别是脊髓的疼痛感觉，从而导致患者异常性疼痛、痛觉过敏和持续疼痛。为了验证这一点，我们首先分析了外周轴切开术对脊髓背角中仅表达于Rexed II层的E-cadherin表达改变的影响。这种表达在轴突切除后第7天暂时消失，在部分轴突再生后第63天重新出现。相比之下，在神经完全变性后，它仍然无法检测到。钙粘蛋白相关蛋白，连环蛋白也被检查。给药NGF恢复了P物质的免疫反应性，已知P物质在外周轴切开术后消失，但不影响E-cadherin和α N-catenin的免疫反应性。其次，为了研究氧化半乳糖凝集素-1对神经再生的详细细胞效应，采用脱细胞自体和同种异体移植模型。结果表明，外源性rhGal-1/Ox可促进雪旺细胞的迁移，并促进运动神经元和感觉神经元的轴突再生，表明Gal-1/Ox是神经元再生初始阶段的关键因素。这些模型将用于进一步研究初级感觉通路的可塑性。

The ultimate aim of this study is to know the plasticity of primary sensory pathways, especially pain sensation in the spinal cord, resulting in allodynia, hyperalgesia, and persistent pain to the patients. To examine this, the effects of peripheral axotomy to the alteration of the expression of E-cadherin which is exclusively expressed inlamina II of Rexed in the spinal cord dorsal horn was firstly analysed. This expression tem porarily disappeared by day 7 after axotomy and reappeared following partial axonal regeneration on day 63. In contrast, it remained undetectable following complete nerve degeneration. Cadherin-associated protein, catenins are also examined. Administration of NGF rescued the immunoreactivity of substance P, which is known to disappear after peripheral axotomy, but not influence that of both E-cadherin and alpha N-catenin. Secondly, to investigate the detailed cellular effects of oxidized galectin-1, which effect to nerve regeneration has been recently identified, acellular auto- and allograft model were utilized. Our results indicated that local application of exogenous rhGal-1/Ox promotes the migration of Schwann cells followed by axonal regeneration from both motor and sensory neurons, and that Gal-1/Ox is a key factor of initial stage of neuronal regeneration. These models would be utilized for further investigation of the plasticity of primary sensory pathways.