Pyrogenic doses of intracerebroventricular interleukin-1 did not induce analgesia in the rat hot-plate or cold-water tail-flick tests.
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-alpha (IFN-alpha) in rats. In the cold-water tail-flick test (CWT), latency to tail withdrawal from a -3 degrees C liquid was timed; in the hot-plate test (HP), latency to a rear paw lick or a jump from a 55 degrees C surface was measured. In some experiments, core body temperature was also monitored with a rectal thermistor. In the CWT, human recombinant (hr) IFN-alpha induced a small, statistically significant effect at just one dose (15,000 U icv), but no dose of hr-IL-1 alpha (250-1000 U icv) or hr-IL-1 beta (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-1 alpha and IL-1 beta. The largest hyperthermic effect was a 1.7 (+/- 0.15) degrees C rise 120 min after administration of 1000 U IL-1 beta. In a second analgesic assay, the HP, IL-1 beta 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 micrograms, icv) induced analgesia in the CWT (32.7 and 61.8% maximum analgesia, respectively); however, there was no significant effect of IL-1 beta 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.
Adams
J U
JU
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
Bussiere
J L
JL
Geller
E B
EB
Adler
M W
MW
D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D009020:Morphine; D010147:Pain Measurement / Q000187:drug effects*; D011749:Pyrogens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D011749:Pyrogens; D009020:Morphine