Effects of Tnf-α injected intracisternally on the nociceptive jaw-opening reflex and orofacial formalin test in freely moving rats

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)-α 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-α, 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-α. However, 20 ng Tnf-α 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-α did not change the number of noxious behavioral responses produced by formalin injection. However, 200 pg Tnf-α 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-α increased formalin induced noxious behavioral responses in only the late phase. A higher dose of 20 ng Tnf-α did not change the number of noxious behavioral responses produced by formalin injection. The hyperalgesic action of Tnf-α injected intracisternally was blocked by pretreatment with the interleukin-1 (IL-1) receptor antagonist. These results suggest that central Tnf-α modulates the transmission of nociceptive information in the orofacial area. However, the hypo/hyperalgesic response of central Tnf-α seems to depend on the orofacial pain model or in a dose-related manner. The hyperalgesic response of central Tnf-α seems to be mediated by the IL-1 receptor.