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Journal of Neural Transplantation and Plasticity
Volume 4, Issue 1, Pages 15-26

Antinociception Following Implantation of AtT-20 and Genetically Modified AtT-20/hENK Cells in Rat Spinal Cord

1Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
2Graduate Program in Neuroscience, Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, MN 55455, USA
3Department of Pharmacology, Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA

Copyright © 1993 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


AtT-20 cells, which produce ß-endorphin, and AtT-20/hENK cells, which are AtT-20 cells transfected with a proenkephalin gene, were implanted in the rat spinal subarachnoid space in an effort to produce an antinociceptive effect. Host rats were tested for antinociceptive activity by standard nociceptive tests, tail flick and hot plate. Although cell implants had minimal effect on the basal response to thermal nociceptive stimuli, administration of the ß2-adrenergic agonist isoproterenol produced antinociception in the cell-implanted group but not in the control group. The antinociceptive effect of isoproterenol was dose-related and could be blocked by the opioid antagonist naloxone. Immunohistochemical analysis of spinal cords revealed the presence of enkephalin-negative cells surrounding the spinal cord of rats receiving AtT-20 cell implants, and enkephalinpositive cells surrounding the spinal cord of rats. receiving AtT-20/hENK cell implants. These results suggest that opioid-releasing cells implanted around rat spinal cord can produce antinociception and may provide an alternative therapy for chronic pain.