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Original article
Ex vivo study of human visceral nociceptors
  1. Cian McGuire1,
  2. George Boundouki2,
  3. James R F Hockley2,
  4. David Reed2,
  5. Vincent Cibert-Goton1,
  6. Madusha Peiris2,
  7. Victor Kung1,
  8. John Broad1,
  9. Qasim Aziz2,
  10. Christopher Chan1,
  11. Shafi Ahmed1,
  12. Mohamed A Thaha1,
  13. Gareth J Sanger1,
  14. L Ashley Blackshaw2,
  15. Charles H Knowles1,
  16. David C Bulmer1
  1. 1National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  1. Correspondence to Dr David Bulmer, Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London E1 2AJ, UK; d.bulmer{at}qmul.ac.uk

Abstract

Objective The development of effective visceral analgesics free of deleterious gut-specific side effects is a priority. We aimed to develop a reproducible methodology to study visceral nociception in human tissue that could aid future target identification and drug evaluation.

Design Electrophysiological (single unit) responses of visceral afferents to mechanical (von Frey hair (VFH) and stretch) and chemical (bradykinin and ATP) stimuli were examined. Thus, serosal afferents (putative nociceptors) were used to investigate the effect of tegaserod, and transient receptor potential channel, vanilloid 4 (TRPV4) modulation on mechanical responses.

Results Two distinct afferent fibre populations, serosal (n=23) and muscular (n=21), were distinguished based on their differences in sensitivity to VFH probing and tissue stretch. Serosal units displayed sensitivity to key algesic mediators, bradykinin (6/14 units tested) and ATP (4/10), consistent with a role as polymodal nociceptors, while muscular afferents are largely insensitive to bradykinin (0/11) and ATP (1/10). Serosal nociceptor mechanosensitivity was attenuated by tegaserod (−20.8±6.9%, n=6, p<0.05), a treatment for IBS, or application of HC067047 (−34.9±10.0%, n=7, p<0.05), a TRPV4 antagonist, highlighting the utility of the preparation to examine the mechanistic action of existing drugs or novel analgesics. Repeated application of bradykinin or ATP produced consistent afferent responses following desensitisation to the first application, demonstrating their utility as test stimuli to evaluate analgesic activity.

Conclusions Functionally distinct subpopulations of human visceral afferents can be demonstrated and could provide a platform technology to further study nociception in human tissue.

  • VISCERAL NOCICEPTION
  • ABDOMINAL PAIN
  • ELECTROPHYSIOLOGY
  • NEUROGASTROENTEROLOGY
  • VISCERAL SENSITIVITY

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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