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References: Pain, Sensitivity, and the Gut

  1. Terminology - International Association for the Study of Pain (IASP) - The official definitions of pain, nociception, nociceptor, and peripheral and central sensitization used in Sections 8.2, 8.3, 8.9, and 8.10. The notes explaining why pain and nociception are different are short and worth reading.

  2. 15.2 Autonomic Reflexes and Homeostasis - OpenStax, Anatomy and Physiology 2e (CC BY 4.0) - Free open textbook section that explains visceral sensation and referred pain, including the heart-to-left-arm example and the shared-spinal-level explanation in Section 8.4.

  3. Physiology of Visceral Pain - Gebhart GF, Bielefeldt K. Comprehensive Physiology, 2016 - A research review explaining why internal organs have sparse, overlapping sensory nerves, why visceral pain is vague and referred, and how sensitization contributes to chronic visceral pain. The abstract is a clear summary.

  4. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome - Ritchie J. Gut, 1973 - The classic balloon study (67 patients, 16 comparison volunteers) behind the "Read the data" table and the Strong Hype Meter card. The abstract also reports where people felt the pain.

  5. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts - Simrén M, et al. Gut, 2018 - Combines balloon testing data from 1,144 patients in five cohorts and shows that higher sensitivity goes with more severe symptoms, even after accounting for anxiety and depression.

  6. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome - Tillisch K, Mayer EA, Labus JS. Gastroenterology, 2011 - Pools brain imaging studies to show which regions (thalamus, insula, anterior midcingulate) respond to gut stretch in everyone and which differ in IBS. Free full text.

  7. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls - Wilder-Smith CH, et al. Gut, 2004 - The small ice-water study analyzed in this chapter's "How to read a gut-brain claim" box. The free full text includes the funding statement.

  8. Central sensitization: implications for the diagnosis and treatment of pain - Woolf CJ. Pain, 2011 - A widely cited review defining central sensitization as a reversible increase in the excitability of central pain neurons and listing visceral pain hypersensitivity among the conditions it may contribute to.

  9. Pain modulation in the spinal cord - Woolf CJ. Frontiers in Pain Research, 2022 - Open-access review that explains Melzack and Wall's gate control theory and argues that its original circuit is now too simple. Useful for Section 8.6.

  10. Multiple psychological factors predict abdominal pain severity in children with irritable bowel syndrome - Hollier JM, et al. Neurogastroenterology & Motility, 2018 (online) - A study of 261 children with IBS showing that pain catastrophizing partly accounts for the link between anxiety and pain severity. A good example of a careful, correlational design.

  11. Prevalence of irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease in remission: a systematic review and meta-analysis - Fairbrass KM, et al. Lancet Gastroenterology & Hepatology, 2020 - Pools studies of 3,169 adults with IBD in remission and finds that about a quarter to a third report IBS-type symptoms. Source for Section 8.9 and the Bedside variation.

  12. Chapter 6: Hearing, Touch, Taste, Smell, and Pain - From Neuron to Bedside (book #1 in this series) - A free refresher on how the nervous system senses touch and pain, if you want more background before Section 8.5.