title: Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity.
abstract: We investigated the involvement of extracellular signal-regulated protein kinases (ERK) within spinal neurons in producing pain hypersensitivity. Within a minute of an intense noxious peripheral or C-fiber electrical stimulus, many phosphoERK-positive neurons were observed, most predominantly in lamina I and IIo of the ipsilateral dorsal horn. This staining was intensity and NMDA receptor dependent. Low-intensity stimuli or A-fiber input had no effect. Inhibition of ERK phosphorylation by a MEK inhibitor reduced the second phase of formalin-induced pain behavior, a measure of spinal neuron sensitization. ERK signaling within the spinal cord is therefore involved in generating pain hypersensitivity. Because of its rapid activation, this effect probably involves regulation of neuronal excitability without changes in transcription.
authors.affiliation: Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Rm 4309, Charlestown, Massachusetts 02129, USA. ji@helix.mgh.harvard.edu
authors.forename: R R
authors.initials: RR
authors.lastname: Ji
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.forename: G J
authors.initials: GJ
authors.lastname: Brenner
authors.forename: C J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005557:Formaldehyde / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006614:Hindlimb; D066298:In Vitro Techniques; D048369:MAP Kinase Kinase 1; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013696:Temperature
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D002211:Capsaicin