Activation of ERK in the rostral ventromedial medulla is involved in hyperalgesia during peripheral inflammation

We have previously shown that the extracellular signal-regulated kinase (ERK) is activated in the rostral ventromedial medulla (RVM) during peripheral inflammation. In the present study, the relationship between ERK signaling in the RVM and pain hypersensitivity was investigated in the rat. Microinjection of U0126, a mitogen-activated protein kinase kinase inhibitor, into the RVM decreased phosphorylated ERK at 7 h after complete Freund's adjuvant (CFA) injection into the hindpaw. The U0126 microinjection also attenuated thermal hyperalgesia in the ipsilateral hindpaw at 24 h after CFA injection. The ipsilateral paw withdrawal latency in the U0126 group (67.9% ± 5.3% vs. baseline, n = 7) was significantly longer than that in the control group (52.0% ± 3.6% vs. baseline, n = 8). These findings suggest that activation of ERK in the RVM contributes to thermal hyperalgesia during peripheral inflammation.