Journal of the peripheral nervous system : JPNS
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J. Peripher. Nerv. Syst. · Jan 1999
Lumbar transplant of neurons genetically modified to secrete galanin reverse pain-like behaviors after partial sciatic nerve injury.
The use of cell lines as biologic "minipumps" to chronically deliver antinociceptive molecules such as the peptide galanin near the pain processing centers of the spinal cord after nerve injury is a newly developing technology for the treatment of neuropathic pain. The neuronal rat cell line, RN33B, derived from E13 brainstem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat preprogalanin (GAL) cDNA and the galanin-synthesizing and -secreting cell line, 33GAL.19, was isolated [1]. The 33GAL.19 cells transfected with the GAL gene expressed immunoreactivity (ir) for the GAL protein and synthesized low levels of GAL-ir at permissive temperature (33 degrees C), when the cells were proliferating, and increased GAL-ir during terminal differentiation at non-permissive temperature (39 degrees C) in vitro. ⋯ Transplants of 33V.1 control cells had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that a chronically applied, low local dose of galanin supplied by transplanted cells near the lumbar spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of transplants of genetically modified neural cell lines that are able to deliver antinociceptive molecules, such as galanin, offers a safe and novel approach to pain management.