Intracerebroventricular injection of interleukin-1 beta induces hyperalgesia in rats.
To determine whether interleukin-1 beta (IL-1 beta) in the brain may modulate nociception, recombinant human IL-1 beta (rhIL-1 beta) (1 pg/kg to 1 microgram/kg) was microinjected into the lateral cerebral ventricle of rats and the latency before initiating the licking of their hindpaws after being placed on a hot plate (50.0 +/- 0.1 degrees C) was measured. A significant reduction of the paw-lick latency was observed after injections of nonpyrogenic doses (10 pg/kg to 1 ng/kg) of rhIL-1 beta, showing a maximal response at a dose of 100 pg/kg which began to appear 5 min after injection, reached a peak within 30 min and then gradually subsided. An increase in the amount of rhIL-1 beta to > 1 ng/kg (up to 1 microgram/kg) had no effect on the nociceptive threshold. The rhIL-1 beta-induced hyperalgesia was completely abolished by pretreatment with an IL-1 receptor antagonist (IL-1ra) or Na salicylate. Similar pretreatment with alpha-melanocyte-stimulating hormone (alpha-MSH) also inhibited the rhIL-1 beta-induced hyperalgesia. However, pretreatment with alpha-helical corticotropin-releasing factor (CRF)9-41 failed to affect it. The results suggest that IL-1 beta in the brain produces hyperalgesia by its receptor-mediated and prostaglandin-dependent action which is sensitive to alpha-MSH. The hyperalgesic action of central IL-1 does not appear to depend on the CRF system.
Oka
T
T
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aou
S
S
Hori
T
T
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012980:Sodium Salicylate / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; C069206:alpha helical corticotropin-releasing hormone; D000521:alpha-MSH; D003346:Corticotropin-Releasing Hormone; D012980:Sodium Salicylate