Determination of cross tolerance in rat spinal cord using intrathecal infusion via sequential mini-osmotic pumps.
Continuous intrathecal (IT) infusion via ALZET mini-osmotic pumps was used to induced spinal tolerance to morphine in the rat. Naloxone (1 mg/kg IP), injected on day 3 of continuous IT morphine (10 micrograms/hr), produced mild withdrawal symptoms in all morphine-treated animals. In rats pretreated with continuous IT morphine (10 micrograms/hr) or saline, systemic morphine (2, 4, 8, 10 and 15 mg/kg IP) produced equivalent, dose-dependent antinociception using the tail-flick and paw pressure tests. The rostral and caudal distribution of methylene blue dye in rat spinal cord was determined on days 1-7 of continuous IT infusion. The dye remained localized near the catheter tip throughout infusion; maximum distribution was 1.5 cm rostrally and 1.0 cm caudally. The data indicate that morphine, infused at the rate of 10 micrograms/hr, does not undergo extensive redistribution in the spinal cord. A sequential, double mini-osmotic pump technique for cross tolerance studies in rat spinal cord is described. In rats pretreated with continuous IT norepinephrine for 4 days, the antinociceptive actions of continuous IT morphine were reduced but not significantly different from saline-pretreated animals. These data suggest that morphine, injected into the spinal cord, does not produce behavioural analgesia by activation of local adrenergic systems.
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D004361:Drug Tolerance; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009619:Nociceptors / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D011957:Receptors, Opioid; D009020:Morphine; D009638:Norepinephrine