Movement-evoked hyperalgesia induced by lipopolysaccharides is not suppressed by glucocorticoids.
Systemic exposure to lipopolysaccharides (LPS) produces a variety of effects, including movement-evoked hyperalgesia that can be measured using the grip force assay in mice. Because both lethality and enhanced sensitivity to cutaneous pain following exposure to endotoxins have each been attributed to inflammatory mediators, we explored the possibility that LPS-induced movement-evoked hyperalgesia is also sensitive to manipulations of glucocorticoids that regulate these other LPS responses. We found that the hyperalgesic effect of LPS (5mg/kg s.c.) in mice that were adrenalectomized did not differ from that in control mice that were sham operated, even though mortality after LPS was potentiated by adrenalectomy. The development of tolerance to the movement-evoked hyperalgesic effect of LPS also did not differ between adrenalectomized and sham-operated control mice. In addition, mifepristone (25mg/kg s.c.), a glucocorticoid antagonist, did not attenuate the hyperalgesic effect of LPS (2mg/kg s.c.), yet this dose of mifepristone was sufficient to enhance the incidence of lethality induced by LPS. Enhancement of glucocorticoid activity by two injections of dexamethasone (1mg/kg s.c.) had no effect on the degree of hyperalgesia in mice injected with LPS (5mg/kg s.c.), yet this dose of dexamethasone was sufficient to attenuate the incidence of mortality induced by LPS in adrenalectomized mice. Finally, morphine (10mg/kg i.p.) reversed the decrease in grip force caused by LPS (5mg/kg i.p.), supporting the interpretation that decreases in grip force produced by LPS reflect muscle hyperalgesia that is not sensitive to glucocorticoids.
Department of Veterinary Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue, Room 295, Animal Science/Veterinary Medicine Building, St. Paul, MN 55108, USA.
Katalin J
KJ
Kovács
Jonathan C
JC
Papic
Alice A
AA
Larson
D000315:Adrenalectomy; D000818:Animals; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009068:Movement / Q000187:drug effects / Q000502:physiology*
D005938:Glucocorticoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides