Antinociception following implantation of AtT-20 and genetically modified AtT-20/hENK cells in rat spinal cord.
AtT-20 cells, which produce beta-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 beta 2-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 enkephalin-positive 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.
Wu
H H
HH
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
McLoon
S C
SC
Wilcox
G L
GL
D000818:Animals; D017690:Cell Transplantation; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D020889:Rolipram; D012636:Secretory Rate / Q000187:drug effects; D013116:Spinal Cord / Q000503:physiopathology*; D013346:Subarachnoid Space; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation; D001615:beta-Endorphin / Q000378:metabolism*
D004745:Enkephalins; D009363:Neoplasm Proteins; D011498:Protein Precursors; D011760:Pyrrolidinones; D011994:Recombinant Proteins; C029992:proenkephalin; D009270:Naloxone; D001615:beta-Endorphin; D020889:Rolipram; D007545:Isoproterenol