The effects of microinjections of recombinant human interleukin-1β (rhIL-1β) into the hypothalamus and neighboring basal forebrain on nociceptive behavior were studied using a hot-plate test in rats. The microinjection of rhIL-1β at doses between 5 pg/kg and 50 pg/kg into the medial part of the preoptic area (MPO) reduced the paw-withdrawal latency. The maximal reduction was obtained 30 min after the injection of rhIL-1β at 20 pg/kg. RhIL-1β (20 pg/kg)-induced hyperalgesia was completely blocked by the simultaneous injection of IL-1 receptor antagonist (IL-1ra, 20 ng/kg), Na salicylate (200 ng/kg) or α-melanocyte-stimulating hormone (α-MSH, 20 ng/kg). The intra-MPO injection of rhIL-1β at doses of less than 5 pg/kg or more than 50 pg/kg (up to 2 ng/kg) had no effect on nociceptive behavior. The microinjection of rhIL-1β (20 pg/kg) into the lateral part of the preoptic area, the median preoptic nucleus and the diagonal band of Broca also reduced the latency. On the other hand, the microinjection of rhIL-1β (20 pg/kg) into the paraventricular nucleus, the lateral hypothalamic area and the septal nucleus had no effect on nociception. The microinjection of rhIL-1β (20 pg/kg-50 pg/kg) into the ventromedial hypothalamus produced a prolongation of the paw-withdrawal latency. A maximal prolongation was obtained 10 min after the injection of rhIL-1β at 50 pg/kg. This reaction was also blocked by the simultaneous injection of IL-1ra (50 ng/kg) and Na salicylate (500 ng/kg). These findings indicate that IL-1β in the MPO and the VMH produces hyperalgesia and analgesia, respectively, while, in addition, both effects are mediated by IL-1 receptors and the synthesis of prostaglandins.
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