Cell therapy for neuropathic pain in spinal cord injuries

Cell therapy to treat neuropathic pain after spinal cord injury (SCI) is in its infancy. However, the development of cellular strategies that would replace or be used as an adjunct to existing pharmacological treatments for neuropathic pain have progressed tremendously over the past 20 years. The earliest cell therapy studies for pain relief tested adrenal chromaffin cells from rat or bovine sources, placed in the subarachnoid space, near the spinal cord pain- processing pathways. These grafts functioned as cellular minipumps, secreting a cocktail of antinociceptive agents around the spinal cord for peripheral nerve injury, inflammatory or arthritic pain. These initial animal, and later clinical, studies suggested that the spinal intrathecal space was a safe and accessible location for the placement of cell grafts. However, one major problem was the lack of a homogeneous, expandable cell source to supply the antinociceptive agents. Cell lines that can be reversibly immortalised are the next phase for the development of a practical, homogenous cell source. These technologies have been modelled with a variety of murine cell lines, derived from embryonic adrenal medulla or CNS brainstem, in which cells are transplanted, which downregulate their proliferative, oncogenic phenotype either before or after transplant. An alternative approach for existing human cell lines is the use of neural or adrenal precursors, in which the antinociceptive properties are induced by in vitro treatment with molecules that move the cells to an irreversible neural or chromaffin, and non-oncogenic, phenotype. Although such human cell lines are at an early stage of investigation, their clinical antinociceptive potential is significant given the daunting problem of difficult-to-treat neuropathic SCI pain.