Inhibition by neuropeptides of interleukin-1 beta-induced, prostaglandin-independent hyperalgesia.
The cytokine interleukin-1 beta (IL-1 beta) is a potent hyperalgesic agent in the rat whereas IL-1 alpha is relatively inactive (Ferreira et al., 1988). IL-1 beta induced a dose-dependent increase in the sensitivity of rat paws to mechanical stimulation following intra-plantar injection but this effect was not reduced by indomethacin (1.0 mg kg-1, p.o.), at a dose known to inhibit completely prostaglandin synthesis in the rat (Salmon et al., 1983). Prostaglandin (PG)E2 enhanced sensitivity to both mechanical pressure and increased temperature but IL-1 beta enhanced only sensitivity to pressure. These observations indicate that IL-1 beta sensitized pressure-sensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism. Hyperalgesia induced by IL-1 beta but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (alpha MSH) and its analogue [Nle4, D-Phe7] alpha MSH which are known to antagonize IL-1 responses in other systems (Holdeman & Lipton, 1985; Cannon et al., 1986). IL-1 beta-induced hyperalgesia was also reduced by the putative IL-1 beta antagonist Lys-D-Pro-Thr (Ferreira et al., 1988) but alpha MSH and its analogue were 10-50 times more potent.
Follenfant
R L
RL
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Nakamura-Craig
M
M
Henderson
B
B
Higgs
G A
GA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D007375:Interleukin-1; D009479:Neuropeptides; D011453:Prostaglandins; D009074:Melanocyte-Stimulating Hormones; D007213:Indomethacin