Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity

We investigated the involvement of extracellular signal-regulated protein k inases (ERK) within spinal neurons in producing pain hypersensitivity. With in a minute of an intense noxious peripheral or C-fiber electrical stimulus , many phosphoERK-positive neurons were observed, most predominantly in lam ina I and IIo of the ipsilateral dorsal horn. This staining was intensity a nd NMDA receptor dependent. Low-intensity stimuli or A-fiber input had no e ffect. Inhibition of ERK phosphorylation by a MEK inhibitor reduced the sec ond phase of formalin-induced pain behavior, a measure of spinal neuron sen sitization. ERK signaling within the spinal cord is therefore involved in g enerating pain hypersensitivity. Because of its rapid activation, this effe ct probably involves regulation of neuronal excitability without changes in transcription.