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Perceptual wind-up in the human oesophagus is enhanced by central sensitisation
  1. S Sarkar1,
  2. C J Woolf2,
  3. A R Hobson1,
  4. D G Thompson1,
  5. Q Aziz1
  1. 1Department of GI Science, Hope Hospital, Salford, University of Manchester, Manchester, UK
  2. 2Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
  1. Correspondence to:
    Dr S Sarkar
    GI Sciences, Clinical Sciences Building, Hope Hospital, Salford M6 8HD, UK; sanchoy{at}


Background: Oesophageal acid infusion induces enhanced pain hypersensitivity in non-acid exposed upper oesophagus (secondary hyperalgesia) in patients with non-cardiac chest pain, thus suggesting central sensitisation contributes to visceral pain hypersensitivity in functional gut disorders (FGD). Perceptual wind-up (increased pain perception to constant intensity sensory stimuli at frequencies ⩾0.3 Hz) is used as a proxy for central sensitisation to investigate pain syndromes where pain hypersensitivity is important (for example, fibromyalgia).

Aims: Wind-up in central sensitisation induced human visceral pain hypersensitivity has not been explored. We hypothesised that if wind-up is a proxy for central sensitisation induced human visceral pain hypersensitivity, then oesophageal wind-up should be enhanced by secondary hyperalgesia.

Methods: In eight healthy volunteers (seven males; mean age 32 years), perception at pain threshold to a train of 20 electrical stimuli applied to the hand and upper oesophagus (UO) at either 0.1 Hz (control) or 2 Hz was determined before and one hour after a 30 minute lower oesophageal acid infusion.

Results: Wind-up occurred only with the 2 Hz train in the UO and hand (both p = 0.01). Following acid infusion, pain threshold decreased (17 (4)%; p = 0.01) in the UO, suggesting the presence of secondary hyperalgesia. Wind-up to the 2 Hz train increased in the UO (wind-up ratio 1.4 (0.1) to 1.6 (0.1); p = 0.03) but not in the hand (wind-up ratio 1.3 (0.1) and 1.3 (0.1); p = 0.3)

Conclusion: Enhanced wind-up after secondary oesophageal hyperalgesia suggests that visceral pain hypersensitivity induced by central sensitisation results from increased central neuronal excitability. Wind-up may offer new opportunities to investigate the contribution of central neuronal changes to symptoms in FGD.

  • NMDA, N-methyl-D-aspartate
  • FGD, functional gut disorders
  • ICC, intraclass correlation
  • CNS, central nervous system
  • VAS, visual analogue scale
  • UO, upper oesophagus
  • CEP, cortical evoked potential
  • central sensitisation
  • wind up
  • visceral hypersensitivity
  • visceral pain
  • temporal summation

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  • Published online first 21 February 2006

  • Conflict of interest: None declared.

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