INTRACEREBROVENTRICULAR INJECTION OF INTERLEUKIN-1-BETA ENHANCES NOCICEPTIVE NEURONAL RESPONSES OF THE TRIGEMINAL NUCLEUS CAUDALIS IN RATS

To assess the effect of interleukin-1 (IL-1) in the brain on nociception electrophysiologically, recombinant human IL-I beta (rhIL-1 beta) (1 pg/kg to 1 mu g/kg, i.e., 0.29 pg-0.33 mu g/rat) was microinjected into the lateral cerebral ventricle of urethane-anesthetized rats and the changes of responses in the wide dynamic range (WDR) neurons in the trigeminal nucleus caudalis to noxious pinching of facial skin were observed. A significant enhancement in the responses of the WDR neurons to noxious stimuli was observed after the injection of rhIL-1 beta between 10 pg/kg and 1 ng/kg, which showed a maximal response at a dose of 100 pg/kg (29-33 pg/rat) which began to appear 5 min after injection, reached a peak within 25 min and then gradually subsided. However, this dose of rhIL-1 beta did not affect the responses of low threshold mechanoreceptive neurons to skin brushing. An increase in the dose of rhIL-1 beta by more than 10 ng/kg (up to 1 beta g/kg) had no effect on the nociceptive responses of the WDR neurons. The rhIL-1 beta-induced enhancement of nociceptive responses of WDR neurons was completely abolished by pretreatment with either IL-1 receptor antagonist, Na salicylate or alpha-melanocyte stimulating hormone. These results therefore provide electrophysiological evidence that IL-1 beta which is produced in the brain induces hyperalgesia in the rat.