The present study was performed to investigate the effects of central cytokines on the modulation of nociception in the orofacial area. A nociceptive jaw-opening reflex (JOR) and an orofacial formalin test were monitored after intracisternal administration of tumor necrosis factor (TNF)-alpha in freely moving rats. Experiments were carried out on 83 male rats weighing 300-350 g and surgical procedures were performed under pentobarbital sodium. After intracisternal injection of Tnf-alpha, digastric electromyogram (dEMG) and noxious behavioral responses were monitored. In the nociceptive JOR, dEMG was not significantly changed after intracisternal injection of 200 pg and 2 ng Tnf-alpha. However, 20 ng Tnf-alpha suppressed dEMG to 72+/-6% of the control values. The orofacial formalin responses showed two distinct phases separated by a time of relative inactivity with an early short-lasting response (0-9 min, first phase) and a continuous prolonged response (10-45 min, second phase). In the inflammatory orofacial formalin test, intracisternal injection of 20 pg Tnf-alpha did not change the number of noxious behavioral responses produced by formalin injection. However, 200 pg Tnf-alpha injected intracisternally significantly increased the number of noxious behavioral responses produced by formalin injection in both the early and late phases, and 2 ng Tnf-alpha increased formalin induced noxious behavioral responses in only the late phase. A higher dose of 20 ng Tnf-alpha did not change the number of noxious behavioral responses produced by formalin injection. The hyperalgesic action of Tnf-alpha injected intracisternally was blocked by pretreatment with the interleukin-1 (IL-1) receptor antagonist. These results suggest that central Tnf-alpha modulates the transmission of nociceptive information in the orofacial area. However, the hypo/hyperalgesic response of central Tnf-alpha seems to depend on the orofacial pain model or in a dose-related manner. The hyperalgesic response of central Tnf-alpha seems to be mediated by the IL-1 receptor.