Intracisternal administration of mitogen-activated protein kinase inhibitors reduced IL-1β-induced mirror-image mechanical allodynia in the orofacial area of rats

The present study investigated the role of central mitogen-activated protein kinases (MAPKs) in interleukin-1β (IL-1β)-induced mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on Sprague-Dawley rats. Under pentobarbital sodium anesthesia, a polyethylene tube was implanted in the subcutaneous area of one vibrissa pad, which enabled us to inject IL-1β. For an intracisternal injection, each anesthetized rat was mounted on a stereotaxic frame and a polyethylene tube was implanted. Animals were given a recovery time of at least 72 h from surgery. After a subcutaneous administration of 0.01, 0.1, 1, or 10 pg of IL-1β, we examined the face withdrawal behavioral responses produced by 10 successive trials of air puffs ipsilateral or contralateral to the IL-1β injection site. Normal animals did not respond to pressure less than 40 psi. The thresholds of air puffs ipsilateral and contralateral to the IL-1β injection site were significantly lower in the IL-1β-treated group, compared with the vehicle-treated group. The decrease in the threshold of air puffs appeared 10 min after an IL-1β injection and persisted for over 3 h. Intracisternal pretreatment with PD98059, a p44/42 MAPK inhibitor, or SB203580, a p38 MAPK inhibitor, significantly reduced the decrease in the threshold of air puffs ipsilateral to the IL-1β injection site produced by 10 pg of IL-1β. IL-1β-induced mirror-image mechanical allodynia was also reduced significantly by intracisternal pretreatment with both PD98059 and SB203580. These results indicate that central MAPK pathways mediate IL-1β-induced mirror-image mechanical allodynia in the orofacial area.