title: The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia.
abstract: BACKGROUND
  The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD).
  
  
  METHODS
  10-day-old male rats received 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3, 1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention.
  
  
  RESULTS
  Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats.
  
  
  CONCLUSIONS
  Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA 94305-5187, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Shenoy
authors.forename: P J
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001418:Baclofen / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004415:Dyspepsia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004576:Electromyography; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D020671:Posterior Horn Cells / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D058785:GABA-A Receptor Agonists; D016760:Proto-Oncogene Proteins c-fos; D001418:Baclofen