Experimental neurology
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Experimental neurology · Apr 2016
Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury.
Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months. ⋯ Notably, satellite glial cells (SGCs) in C6-C8 DRGs exhibited increases in GFAP and connexin-43, suggesting ongoing peripheral sensitization. Carbenoxolone, a gap junction inhibitor, and specific peptide inhibitors of connexin-43, ameliorated established tactile allodynia after severe SCI. Collectively, severe T3 SCI successfully models persistent pain states and could constitute a useful model system for examining candidate translational pain therapies after SCI.
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Experimental neurology · Apr 2016
Adult skin-derived precursor Schwann cells exhibit superior myelination and regeneration supportive properties compared to chronically denervated nerve-derived Schwann cells.
Functional outcomes following delayed peripheral nerve repair are poor. Schwann cells (SCs) play key roles in supporting axonal regeneration and remyelination following nerve injury, thus understanding the impact of chronic denervation on SC function is critical toward developing therapies to enhance regeneration. To improve our understanding of SC function following acute versus chronic-denervation, we performed functional assays of SCs from adult rodent sciatic nerve with acute- (Day 5 post) or chronic-denervation (Day 56 post), versus embryonic nerves. ⋯ Interestingly, aSKP-SCs closely resembled acutely injured and embryonic SCs, exhibiting elevated expression of these same transcription factors. In summary, prolonged denervation resulted in SC deficiency in several functional parameters that may contribute to impaired regeneration. In contrast, aSKP-SCs closely resemble the regenerative attributes ascribed to acutely-denervated or embryonic SCs emphasizing their potential as an accessible and autologous source of glia cells to enhance nerve regeneration, particularly following delays to surgical repair.