title: Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-methyl-D-aspartate receptors.
abstract: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the pathophysiological mechanisms of the pain and hypersensitivity are incompletely understood. IBS patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting involvement of central hyperalgesic mechanisms. We tested the role of tonic peripheral impulse input by using both repetitive thermal stimuli to the leg and repetitive stimuli to the rectum. Changes in thermal/visceral pain sensitivity after nociceptive thermal/visceral repetitive stimulation were determined. A subset of IBS patients showed enhanced rectal/thermal pain sensitivity after repetitive thermal/rectal stimulation, respectively. IBS patients then received 60 mg dextromethorphan and placebo (diphenhydramine) in a randomized, double-blind, crossover trial. The results showed that 1) a subset of IBS patients had increased visceral/cutaneous hypersensitivity following a series of repetitive nociceptive stimuli and that 2) this increased pain sensitivity was blocked by administration of dextromethorphan. This is the first human study indicating that repetitive stimulation enhances a bidirectional mechanism of secondary hyperalgesia due to viscerosomatic facilitation in IBS patients. These unique findings elucidate mechanisms of somatic hypersensitivity in IBS patients and support an etiologic basis for abnormal N-methyl-D-aspartate receptor mechanisms that may be the target of future therapies for IBS.
  
  
  CONCLUSIONS
  Repetitive stimulation enhances a bidirectional mechanism of secondary hyperalgesia due to viscerosomatic convergence in IBS patients. The findings elucidate unique mechanisms of somatic/visceral hypersensitivity in a subset of IBS patients and further support an etiologic basis for abnormal N-methyl-D-aspartate receptor mechanisms that may be future targets of therapies for IBS.
authors.affiliation: Department of Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0764, USA.
authors.forename: G Nicholas
authors.initials: GN
authors.lastname: Verne
authors.forename: Donald D
authors.initials: DD
authors.lastname: Price
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Callam
authors.forename: Buyi
authors.initials: B
authors.lastname: Zhang
authors.forename: Josh
authors.initials: J
authors.lastname: Peck
authors.forename: QiQi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000328:Adult; D001007:Anxiety / Q000209:etiology; D003863:Depression / Q000209:etiology; D003915:Dextromethorphan / Q000627:therapeutic use*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D043183:Irritable Bowel Syndrome / Q000145:classification* / Q000188:drug therapy / Q000503:physiopathology; D007866:Leg / Q000294:innervation; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000523:psychology; D010812:Physical Stimulation / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012007:Rectum / Q000294:innervation; D059265:Visceral Pain / Q000188:drug therapy* / Q000209:etiology; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan