Inhibition by neuropeptides of interleukin‐1β‐induced, prostaglandin‐independent hyperalgesia

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Abstract
The cytokine interleukin-1β (IL-lβ) is a potent hyperalgesic agent in the rat whereas IL-1α is relatively inactive (Ferreira et al., 1988). IL-1β 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-1β enhanced only sensitivity to pressure. These observations indicate that IL-1β sensitized pressure-sensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism. Hyperalgesia induced by IL-1β but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (αMSH) and its analogue [Nle4, D-Phe7] αMSH which are known to antagonize IL-1 responses in other systems (Holdeman & Lipton, 1985; Cannon et al., 1986). IL-1β induced hyperalgesia was also reduced by the putative IL-1β antagonist Lys-D-Pro-Thr (Ferreira et al., 1988) but αMSH and its analogue were 10–50 times more potent.