Intracisternal administration of chemokines facilitated formalin-induced behavioral responses in the orofacial area of freely moving rats

The present study investigated the effects of intracistemal administration of MCP-1, Rantes or IL-8 on pain transmission in the orofacial area. We also investigated mechanisms of hyperalgesic responses produced by intracistemal administration of IL-8. An orofacial formalin test was employed to assess the effects of chemokines on nociceptive processing. For each animal, the number of behavioral responses and the time spent grooming, rubbing and/or scratching the facial region proximal to the formalin injection site was recorded for nine successive 5-min intervals. Intracistemal administration of MCP-1, Rantes or IL-8 significantly increased formalin-induced scratching behavioral responses in the orofacial area. Intracistemal pretreatment with indomethacin, a non-selective cyclooxygenase inhibitor, did not block IL-8-induced hyperalgesia. Pretreatment with 100 μg propranolol, a non-selective β-adrenergic receptor antagonist and 50 μg atenolol, a selective β₁- adrenergic receptor antagonist, inhibited the number of scratches and the duration of scratching produced by 1 ng of IL-8 injected intracisternally. These results indicate that intracistemal administration of chemokines produce a hyperalgesic response with an orofacial inflammatory pain model and that the IL-8-induced hyperalgesia is mediated by central β₁-adrenergic receptor.