title: Epidural administration of liposome-encapsulated hydromorphone provides extended analgesia in a rodent model of stifle arthritis.
abstract: Liposome encapsulation of opioids by using an ammonium-sulfate-gradient loading technique significantly slows the release time of the drug. This study evaluated the duration of analgesia in a rodent model of monoarthritis after epidural administration of liposome-encapsulated hydromorphone (LE-hydromorphone; prepared by ammonium-sulfate-gradient loading) compared with standard hydromorphone and a negative control of blank liposomes. Analgesia was assessed by changes in thermal withdrawal latency, relative weight-bearing, and subjective behavioral scoring. Analgesia in arthritic rats was short-lived after epidural hydromorphone; increases in pain threshold were observed only at 2 h after administration. In contrast, thermal pain thresholds after epidural LE-hydromorphone were increased for as long as 72 h, and subjective lameness scores were lower for as long as 96 h after epidural administration. Injection of LE-hydromorphone epidurally was associated with various mild changes in CNS behavior, and 2 rats succumbed to respiratory depression and death. In conclusion, LE-hydromorphone prolonged the duration of epidural analgesia compared with the standard formulation of hydromorphone, but CNS side effects warrant careful administration of this LE-hydromorphone in future studies.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Schmidt
authors.forename: Lisa
authors.initials: L
authors.lastname: Krugner-Higby
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Heath
authors.forename: Ruth
authors.initials: R
authors.lastname: Sullivan
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Smith
mesh_terms: D015360:Analgesia, Epidural / Q000379:methods*; D000704:Analysis of Variance; D000818:Animals; D001168:Arthritis / Q000150:complications* / Q000473:pathology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004091:Hydromorphone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008081:Liposomes / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D051381:Rats; D013116:Spinal Cord / Q000473:pathology; D013264:Stifle / Q000473:pathology*
chemical_list: D003692:Delayed-Action Preparations; D008081:Liposomes; D004091:Hydromorphone