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J Neurotrauma. 2018 Nov 1;35(21):2561-2571. doi: 10.1089/neu.2017.5537. Epub 2018 Jul 23.

The Amelioration of Pain-Related Behavior in Mice with Chronic Spinal Cord Injury Treated with Neural Stem/Progenitor Cell Transplantation Combined with Treadmill Training.

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1 Department of Rehabilitation Medicine, Keio University School of Medicine , Tokyo, Japan .
2 Department of Orthopaedic Surgery, Keio University School of Medicine , Tokyo, Japan .
3 Department of Physiology, Keio University School of Medicine , Tokyo, Japan .
4 Department of Orthopaedic Surgery, Murayama Medical Center , National Hospital Organization, Tokyo, Japan .


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.


allodynia; exercise; neuropathic pain; regenerative medicine; rehabilitation; sensory function


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