An experimental study of viscero-visceral hyperalgesia using an ultrasound-based multimodal sensory testing approach.
Abstract
Widespread visceral hypersensitivity and the overlap of symptom complexes observed in functional gastrointestinal disorders may be related to central sensitization and neuroplastic changes. A multimodal and multi-segmental model was developed to evaluate viscero-visceral hyperalgesia induced by experimental esophageal sensitization in healthy volunteers. Twelve healthy subjects were studied using a double-blinded, placebo-controlled design. The sensitivity to mechanical and heat stimulations was assessed in the proximal esophagus, duodenum and rectum before and after perfusion of the distal esophagus with acid or saline. A special-designed probe was used allowing cross-sectional ultrasound imaging during mechanical and heat stimulation of the esophagus and duodenum. Another probe was used for mechanical stimulation of the rectum. The referred somatic pain areas to gut pain stimulations were also assessed. Following acid perfusion 11 of 12 volunteers showed increased sensitivity to one or more stimulation modalities. An overall increased sensitivity to mechanical stretch in the three gut segments was seen (P=0.0001). Posthoc analysis showed that this was mainly due to increased sensitivity in the rectum (P<0.001). No changes were seen to thermal stimulations (all P-values>0.4). The somatic referred pain area to duodenal stimulations increased (P=0.04), while it was unaffected to esophageal and rectal stimulations (P>0.3). The present method demonstrated a new approach to assess multimodal sensitivity to experimental sensitization of the esophagus and related viscero-visceral hyperalgesia. Central mechanisms can explain the remote hyperalgesia to mechanical visceral stimulation and the increase in referred pain areas. The present method may be used to explore pathophysiology and pharmacological interventions in patients with visceral hypersensitivity.
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Increased nociceptive activity produces changes in the excitability of spinal neurons (central sensitization), which can expand from spinal segments where the fibers enter to more remote regions.
“This increased nociceptive activity in turn produces changes in the excitability of spinal neurons, a phenomenon called central sensitization [19], [20], which can expand from spinal segments where the fibers enter to more remote regions [21].”
From Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis (2012) · cites this paper as [21]
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“remote regions [21].”
- Authors
- Frøkjær, J. B., Andersen, S. D., Gale, J., Arendt-Nielsen, L., Gregersen, H., & Drewes, A. M.
- Affiliations
- Aalborg University Hospital (DK)
- Pfizer (United Kingdom) (GB)
- Venue
- Pain
- Published
- 2005-12
- Volume
- 119
- Issue
- 1-3
- Pages
- 191-200
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W1974771551
- Cited by
- 51
- References
- 41
- Citations by year
- 2024: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Funders
- Pfizer
- Olympus
- Fresenius Kabi
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- visceral hypersensitivity, central sensitization, ultrasonic probe, thermal sensitivity, rectum, duodenum, functional gastrointestinal disorders, neuroplasticity
- MeSH terms
- Adult, Duodenum, Esophagus, Female, Humans, Hyperalgesia, Image Interpretation, Computer-Assisted, Male, Middle Aged, Pain Measurement, Physical Stimulation, Rectum, Sodium Chloride, Viscera, Abdominal Pain, Endosonography, Gastrointestinal Tract
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