title: No detectable analgesic effects in the formalin test even with one million bovine adrenal chromaffin cells.
abstract: The present experiments were conducted to identify analgesic agents for transfection into immortalized adrenal chromaffin cell lines to maximize their analgesic potential. Analgesic agents known to be produced by adrenal chromaffin cells were infused intrathecally at a low dose (0.2 microg) which might conceivably be attained by adrenal chromaffin cell transplants. Numerous agents, administered individually and in two-factor combinations, produced significant analgesic effects in the formalin test. Before assessing the potential additive or synergistic effects of these analgesic agents with adrenal chromaffin cells, studies were conducted to demonstrate analgesic effects with adrenal chromaffin cells alone. Analgesic effects were previously reported in the literature with 80-100k intrathecal bovine adrenal chromaffin (BAC) cells; but in the present study 500k purified BAC cells failed to produce detectable analgesic effects. One million purified BAC cells also failed to produce analgesic effects in the formalin test. In a final study, even nicotine-stimulated release from one million purified BAC cells failed to produce analgesic effects in the formalin test. The fact that even one million nicotine-stimulated BAC cells failed to demonstrate therapeutic potential in these blinded experiments under conditions which were clearly sensitive to the analgesic agents produced by BAC cells, raises serious questions about the clinical utility of this experimental treatment.
authors.affiliation: CytoTherapeutics, Inc, Two Richmond Square, Providence, RI 02906, USA.
authors.forename: Amit G
authors.initials: AG
authors.lastname: Gulwadi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hoane
authors.forename: Joel A
authors.initials: JA
authors.lastname: Saydoff
authors.forename: Beata R
authors.initials: BR
authors.lastname: Frydel
authors.forename: Mark D
authors.initials: MD
authors.lastname: Lindner
mesh_terms: D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002452:Cell Count; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D007278:Injections, Spinal; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D010147:Pain Measurement; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord; D013268:Stimulation, Chemical
chemical_list: D000700:Analgesics; D018722:Nicotinic Agonists; D018847:Opioid Peptides; D011506:Proteins; C082312:histogranin; D009538:Nicotine; D009638:Norepinephrine