Attenuation of SCI-Induced Hypersensitivity by Intensive Locomotor Training and Recombinant GABAergic Cells

The underlying mechanisms of spinal cord injury (SCI)-induced chronic pain involve dysfunctional GABAergic signaling and enhanced NMDA signaling. Our previous studies showed that SCI hypersensitivity in rats can be attenuated by recombinant rat GABAergic cells releasing NMDA blocker serine-histogranin (SHG) and by intensive locomotor training (ILT). The current study combines these approaches and evaluates their analgesic effects on a model of SCI pain in rats. Cells were grafted into the spinal cord at 4 weeks post-SCI to target the chronic pain, and ILT was initiated 5 weeks post-SCI. The hypersensitivity was evaluated weekly, which was followed by histological and biochemical assays. Prolonged effects of the treatment were evaluated in subgroups of animals after we discontinued ILT. The results show attenuation of tactile, heat and cold hypersensitivity in all of the treated animals and reduced levels of proinflammatory cytokines IL1 beta and TNF alpha in the spinal tissue and CSF. Animals with recombinant grafts and ILT showed the preservation of analgesic effects even during sedentary periods when the ILT was discontinued. Retraining helped to re-establish the effect of long-term training in all of the groups, with the greatest impact being in animals with recombinant grafts. These findings suggest that intermittent training in combination with cell therapy might be an efficient approach to manage chronic pain in SCI patients.

Automated summary

This study found that chronic pain caused by spinal cord injury is related to dysfunctional GABAergic signaling and enhanced NMDA signaling. In a rat model, grafting recombinant rat GABAergic cells into the spinal cord and intensive locomotor training can reduce pain sensitivity. These treatments can attenuate tactile, heat, and cold hypersensitivity and reduce levels of proinflammatory cytokines. The analgesic effects of cell therapy and locomotor training persist even after the training is discontinued. Therefore, intermittent training combined with cell therapy may be an effective approach to manage chronic pain in spinal cord injury patients.