Intracerebroventricular injection of isoproterenol produces its analgesic effect through interleukin-1 beta production

The effects of isoproterenol, a beta-adrenoceptor agonist, on the production of interleukin-lp in the brain and on mechanical nociception were examined in rats. Intracerebroventricular (i.c.v.) injection of isoproterenol at the dose of 3 mu g/rat markedly induced interleukin-1 beta mRNA in the molecular layer of the hippocampus, medial preoptic area, paraventricular thalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus and central gray 1 h after injection. In these regions, interleukin-1 beta mRNA was expressed mainly in the glial cells. The thresholds to the mechanical stimulation to the hind paw were elevated by i.c.v. administration of isoproterenol (1 to 10 mu g/rat). When isoproterenol was given at the dose of 3 mu g/rat, the analgesic effect showed two peaks. The first peak was observed at 60 min after injection and the second was observed at 180 min. The second phase of analgesia was antagonized by coadministration of interleukin-l receptor antagonist. These results suggest that isoproterenol produces an analgesic effect, at least in part, through the induction of interleukin-1 beta expression in the brain. (C) 1997 Elsevier Science B.V.