1 Department of Rehabilitation Medicine, Keio University School of Medicine , Tokyo, Japan .
2 Department of Orthopaedic Surgery, Keio University School of Medicine , Tokyo, Japan .
J Neurotrauma. 2018 Nov 1;35(21):2561-2571. doi: 10.1089/neu.2017.5537. Epub 2018 Jul 23.
Progress in regenerative medicine is realizing the possibility of neural regeneration and functional recovery in spinal cord injury (SCI). Recently, rehabilitation has attracted much attention with respect to the synergistic promotion of functional recovery in combination with neural stem/progenitor cell (NS/PC) transplantation, even in the chronic refractory phase of SCI. Nevertheless, sensory disturbance is one of the most prominent sequelae, even though the effects of combination or single therapies have been investigated mostly in the context of motor recovery. To determine how combination therapy with treadmill training (TMT) and NS/PC transplantation affects the manifestation of thermal allodynia and tactile hyperalgesia in chronic phase SCI, four groups of SCI mice were used to assess pain-related behavior and histological changes: combined transplantation and TMT therapy, transplantation only, TMT only, and control groups. Thermal allodynia and coarse touch-pressure hyperalgesia exhibited significant recovery in the combined therapy group in comparison with controls, whereas there were no significant differences with fine touch-pressure hyperalgesia and motor function. Further investigation revealed fewer fibers remaining in the posterior funiculus, which contained the tracts associated with the two modalities showing less recovery; that is, touch-pressure hyperalgesia and motor function. A significant correlation was only observed between these two modalities. Although no remarkable histological recovery was found within the lesion epicenter, changes indicating amelioration of pain were observed in the lumbar enlargement of the combination therapy group. Our results suggest that amelioration of thermal allodynia and tactile hyperalgesia can be brought about by the additive effect of NS/PC transplantation and TMT. The degree of recovery seems dependent on the distribution of damage.
再生医学的进展正在实现脊髓损伤 (SCI) 中神经再生和功能恢复的可能性。最近，康复治疗结合神经干细胞/祖细胞 (NS/PC) 移植在 SCI 的慢性难治期也引起了很大的关注，以促进功能恢复的协同作用。然而，感觉障碍是最突出的后遗症之一，尽管已经研究了组合或单一疗法对运动恢复的影响。为了确定联合跑步机训练 (TMT) 和 NS/PC 移植治疗对慢性期 SCI 热感觉过敏和触觉痛觉过敏表现的影响，使用四组 SCI 小鼠来评估与疼痛相关的行为和组织学变化：联合移植和 TMT 治疗、移植仅、TMT 仅和对照组。与对照组相比，联合治疗组的热感觉过敏和粗触压痛觉过敏表现出明显的恢复，而精细触压痛觉过敏和运动功能没有明显差异。进一步的研究表明，在后索中仍有较少的纤维残留，这些纤维包含与两种模式相关的恢复较差的束；即触压痛觉过敏和运动功能。仅观察到这两种模式之间存在显著相关性。虽然在损伤中心没有发现明显的组织学恢复，但在联合治疗组的腰椎扩大部观察到了改善疼痛的变化。我们的结果表明，NS/PC 移植和 TMT 的附加效应可以改善热感觉过敏和触觉痛觉过敏。恢复程度似乎取决于损伤的分布。
