title: Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats.
abstract: OBJECTIVE
  Changes in the properties of visceral sensory neurons contribute to the development of gastrointestinal pain. However, little is known about the molecules involved in mechanosensation from the gastrointestinal tract. We investigated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase cascade, in dorsal root ganglion (DRG) and nodose ganglion (NG) neurons by noxious gastric distention (GD) and its involvement in acute visceral pain in rats.
  
  
  METHODS
  Electromyographic responses to gastric balloon distention through gastrostomy were recorded from the acromiotrapezius muscle in rats after splanchnic nerve resection or vagotomy and in control rats. We then examined the phosphorylated-ERK1/2 (p-ERK1/2) labeling in the DRG and NG after GD using immunohistochemistry.
  
  
  RESULTS
  Gastric distention induced p-ERK1/2 in DRG and NG neurons with a peak at 2 minutes after stimulation. We found a stimulus intensity-dependent increase in the number of activated neurons, and this activation corresponded well with the incidence of the visceromotor response. Most of these p-ERK1/2-labeled neurons were small- and medium-sized neurons that coexpressed transient receptor potential vanilloid 1 ion channel and acid-sensing ion channel 3. Splanchnic nerve resection, but not vagotomy, affected the visceromotor response, and attenuated the ERK1/2 activation in DRG neurons produced by GD. Furthermore, intrathecal administration of the mitogen-activated protein kinase kinase 1/2 inhibitor, U0126, altered the response to noxious GD.
  
  
  CONCLUSIONS
  The activation of ERK1/2 pathways in DRG neurons by noxious GD may be correlated with functional activity, and may be involved in acute visceral pain.
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
authors.forename: Koichi
authors.initials: K
authors.lastname: Obata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Kan
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D015746:Abdominal Pain / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D062565:Acid Sensing Ion Channels; D000208:Acute Disease; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002404:Catheterization / Q000009:adverse effects*; D004195:Disease Models, Animal; D004576:Electromyography; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000201:enzymology / Q000503:physiopathology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D009620:Nodose Ganglion / Q000201:enzymology / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism; D013270:Stomach / Q000201:enzymology / Q000294:innervation* / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels; D002070:Butadienes; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009570:Nitriles; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C113580:U 0126; C051774:neurofilament protein H; D048052:Mitogen-Activated Protein Kinase 3