Pyrogenic doses of intracerebroventricular interleukin-1 did not induce analgesia in the rat hot-plate or cold-water tail-flick tests

Abstract

There are a few reports in the literature that cytokines can induce analgesia (5, 6, 18). The present study sought to characterize the analgesic effects of intracerebroventricularly (icv) administered interleukin-1 (IL-1) and interferon-α (IFN-α) in rats. In the cold-water tail-flick test (CWT), latency to tail withdrawal from a -3°C liquid was timed; in the hot-plate test (HP), latency to a rear paw lick or a jump from a 55°C surface was measured. In some experiments, core body temperature was also monitored with a rectal thermistor. In the CWT, human recombinant (hr) IFN-α induced a small, statistically significant effect at just one dose (15,000 U icv), but no dose of hr-IL-1α (250-1000 U icv) or hr-IL-1β (125-2000 U icv) induced a significant effect at any time point. On the other hand, dose-related increases in body temperature were observed after icv injection of both IL-1α and IL-1β. The largest hyperthermic effect was a 1.7 (±0.15) °C rise 120 min after administration of 1000 U IL-1β. In a second analgesic assay, the HP, IL-1β was ineffective as well. Since IL-1 alone did not induce analgesia, we tested its capacity to potentiate morphine analgesia. Morphine (5.0 and 10 μg, icv) induced analgesia in the CWT (32.7 and 61.8% maximum analgesia, respectively); however, there was no significant effect of IL-1β on morphine-induced analgesia. In summary, we failed to find an analgesic effect of IL-1, alone or in combination with morphine, at doses which clearly had a physiological effect; this is in contrast to the reports cited above. © 1993.