The present study was performed to investigate the effects of central cytokines on the modulation of nociception in the orofacial area. To achieve this purpose, a nociceptive jaw opening reflex and an orofacial formalin test were monitored before and after intracisternal administration of interleukin-6 (IL-6) in freely moving rats. In the nociceptive jaw opening reflex, the digastric electromyogram (dEMG) was not significantly changed after intracisternal injection of 200 pg and 2 ng IL-6. However, 20 ng IL-6 suppressed dEMG to 74+/-7% of the control values. In the inflammatory orofacial formalin test, intracisternal injection of 200 pg and 2 ng IL-6 did not change the number of noxious behavioral responses produced by formalin injection. However, 20 ng IL-6 injected intracisternally significantly increased the number of noxious behavioral responses produced by formalin. The hyperalgesic action of intracisternal IL-6 in the orofacial formalin test was blocked by pretreatment with interleukin-1 (IL-1) receptor antagonist. These results suggest that IL-6 injected intracisternally modulates the transmission of nociceptive information in the orofacial area. However, the hypo/hyper-algesic response of central cytokines seems to depend on the orofacial pain model. The hyperalgesic response of central IL-6 seems to be mediated by the IL-1 receptor.