Enhanced thermal antinociceptive potency and anti-allodynic effects of morphine following spinal administration of endotoxin.
Recently, an animal model of central inflammation characterized by widespread cutaneous hyperalgesia and allodynia following intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) was described. In the present study, we demonstrate that central administration of LPS via intrathecal (i.t.) injection produces bilateral tactile allodynia and thermal hyperalgesia in the rat. Also, the effects of morphine-induced antinociception were determined in this model. Here we demonstrate enhanced thermal antinociceptive potency of i.t. morphine in LPS-treated rats compared to controls. Intrathecal morphine was also effective in alleviating the tactile allodynia induced by LPS. Both the antinociceptive and anti-allodynic effects produced by i.t. morphine were completely antagonized by pretreatment with subcutaneous naloxone (1 mg x kg(-1)). This study demonstrates the presence of both heat hyperalgesia and mechanical allodynia following central administration of LPS, and an increased antinociceptive potency of i.t. morphine in this model.
Cahill
Catherine M
CM
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont, Canada.
Dray
Andy
A
Coderre
Terence J
TJ
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced* / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects
D000701:Analgesics, Opioid; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D009020:Morphine