Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-methyl-D-aspartate receptors

G. Nicholas Verne, Donald D. Price, Christopher S. Callam, Buyi Zhang, Josh Peck, Qiqi Zhou

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. Perspective: 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.

Original languageEnglish (US)
Pages (from-to)901-909
Number of pages9
JournalJournal of Pain
Volume13
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Irritable Bowel Syndrome
N-Methyl-D-Aspartate Receptors
Hot Temperature
Hypersensitivity
Dextromethorphan
Pain
Hyperalgesia
Visceral Pain
Diphenhydramine
Body Regions
Rectum
Cross-Over Studies
Leg
Placebos

Keywords

  • dextromethorphan
  • Irritable bowel syndrome (IBS)
  • NMDA receptor
  • repetitive afferent barrage
  • visceral and thermal hypersensitivity
  • viscerosomatic facilitation

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-methyl-D-aspartate receptors. / Verne, G. Nicholas; Price, Donald D.; Callam, Christopher S.; Zhang, Buyi; Peck, Josh; Zhou, Qiqi.

In: Journal of Pain, Vol. 13, No. 9, 09.2012, p. 901-909.

Research output: Contribution to journalArticle

Verne, G. Nicholas ; Price, Donald D. ; Callam, Christopher S. ; Zhang, Buyi ; Peck, Josh ; Zhou, Qiqi. / Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-methyl-D-aspartate receptors. In: Journal of Pain. 2012 ; Vol. 13, No. 9. pp. 901-909.
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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. Perspective: 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.",
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