title: Intrathecal polymer-encapsulated bovine adrenal chromaffin cells fail to produce analgesic effects in the hotplate and formalin test.
abstract: Numerous publications have reported that adrenal chromaffin cells implanted in the lumbar intrathecal space produce analgesic effects in rodent models of pain. The present study was intended to replicate and extend on the results of those previous publications. This study was conducted to determine: (1) if analgesic effects of polymer-encapsulated intrathecal adrenal chromaffin cells could be detected in the more sensitive low temperature hot-plate test without using nicotine to stimulate chromaffin cell output, (2) if a dose-response curve can be produced in the hot-plate and formalin tests with different numbers of adrenal chromaffin cells (0K, 120K, or 330K), (3) if cell viability and/or the magnitude of analgesic effects are affected by differences in implant site (i.e. thoracic versus lumbar implant site), and (4) the magnitude of the analgesic effects of adrenal chromaffin cells relative to doses of systemic morphine. No analgesic effects related to chromaffin cells were detected in the present study in the formalin test or in the hot-plate test, even with nicotine stimulation, regardless of the number of cells implanted or the intrathecal implant site. The reliability and sensitivity of the behavioral measures to the effects of mild analgesics are supported by the fact that consistent differences in performance between individual rats could be detected, the effects of fairly modest doses of nicotine and morphine were detectable, and consistent dose-response curves were evident with respect to both nicotine and morphine. Device performance appeared to be within the range of previous studies that reported analgesic effects of encapsulated adrenal chromaffin cells. It is unclear why analgesic effects of adrenal chromaffin cells were not detected in the present study.
authors.affiliation: CytoTherapeutics, Inc., Two Richmond Square, Providence, Rhode Island 02906, USA. mlindner@neurocrine.com [corrected]
authors.forename: M D
authors.initials: MD
authors.lastname: Lindner
authors.forename: J M
authors.initials: JM
authors.lastname: Francis
authors.forename: J A
authors.initials: JA
authors.lastname: Saydoff
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002214:Capsules; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism* / Q000637:transplantation; D007278:Injections, Spinal; D008161:Lumbosacral Region; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects*; D011108:Polymers; D051381:Rats
chemical_list: D000701:Analgesics, Opioid; D002214:Capsules; D018722:Nicotinic Agonists; D011108:Polymers; D009538:Nicotine; D009020:Morphine; D009638:Norepinephrine