BIPHASIC EFFECTS OF INTRACEREBROVENTRICULAR INTERLEUKIN-1-BETA ON MECHANICAL NOCICEPTION IN THE RAT

The effects of interleukin-1 beta on the mechanical nociceptive thresh old in the rat were examined using the paw-pressure test. An intracere broventricular (i.c.v.) injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia to mechanical stimuli. Higher dose s of interleukin-1 beta (1 and 10 ng/rat) induced an analgesic effect. The coadministration of the interleukin-1 receptor antagonist complet ely antagonized the hyperalgesic and analgesic effects of interleukin- 1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing f actor [9-41] 15 min prior to interleukin-1 beta administration complet ely blocked the hyperalgesic and analgesic effects of interleukin-1 be ta. An i.c.v. injection of sodium salicylate 15 min prior to interleuk in-1 beta administration inhibited the hyperalgesic effect of interleu kin-1 beta, but not the analgesic effect. These results suggest that i nterleukin-1 beta produces biphasic effects on the mechanical nocicept ive threshold through the interleukin-l receptor in the brain and that a corticotropin-releasing factor-mediated pathway is involved. Furthe rmore, the hyperalgesic effect of interleukin-1 beta may be mediated b y prostaglandins.