OESOPHAGUS

Perceptual wind-up in the human oesophagus is enhanced by central sensitisation

S Sarkar¹, C J Woolf², A R Hobson¹, D G Thompson¹, Q Aziz¹

¹ Department of GI Science, Hope Hospital, Salford, University of Manchester, Manchester, UK
² Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

Correspondence to:
Dr S Sarkar
GI Sciences, Clinical Sciences Building, Hope Hospital, Salford M6 8HD, UK; sanchoy{at}aol.com

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.

Abbreviations: 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

Keywords: central sensitisation; wind up; visceral hypersensitivity; visceral pain; temporal summation

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