Aktuelle Ernährungsmedizin 2023; 48(01): 37-45
DOI: 10.1055/a-1976-9382
Übersicht

Wenn aus einem Bauchgefühl viszerale Schmerzen werden: Placebo- und Nocebo-Mechanismen entlang der Darm-Hirn-Achse

When gut feelings turn into visceral pain: Placebo and nocebo mechanisms along the gut-brain axis
Robert Jan Pawlik
1   Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum Medizinische Fakultät, Bochum, Germany
,
JanaLuisa Aulenkamp
2   Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Essen, Germany
3   Klinik für Neurologie, Zentrum für Translationale Neuro- und Verhaltenswissenschaften, Universitätsklinikum Essen, Essen, Germany
,
Sigrid Elsenbruch
1   Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum Medizinische Fakultät, Bochum, Germany
3   Klinik für Neurologie, Zentrum für Translationale Neuro- und Verhaltenswissenschaften, Universitätsklinikum Essen, Essen, Germany
› Author Affiliations
Funding Die Inhalte dieses Übersichtsbeitrages wurden durch die von der Deutschen Forschungsgemeinschaft geförderten Sonderforschungsbereiche (SFB/TRR) 289 ‚Behandlungserwartung‘ (Projekt- ID 422744262)und SFB 1280 ‚Extinktionslernen‘ (Projekt-ID 316803389) angeregt und unterstützt. Für den/die interessierte/n LeserIn siehe www.treatment-expectation.de; https://sfb1280. ruhr-uni-bochum.de.

Zusammenfassung

Das Erleben von Schmerz ist nach heutigem Verständnis durch eine Vielzahl biologischer, psychologischer und sozialer Faktoren geprägt und somit eine komplexe, von der Nozizeption abzugrenzende, psychologische Erfahrung. Entsprechend ist das Schmerzerleben durch psychologische Faktoren modulierbar und chronische Schmerzen werden als biopsychosoziale Erkrankungen verstanden. Dies gilt auch für den Viszeralschmerz, dem spezifische psychophysiologische Prinzipien und neurobiologische Mechanismen zugrunde liegen, was eine interdisziplinäre Betrachtung unter Einbeziehung der Psychologie und der Neurowissenschaften erforderlich macht. Ausgehend von den bidirektionalen Verbindungen zwischen Darm und Hirn und aufbauend auf einem biopsychosozialen Krankheitsmodell beschreibt dieser Übersichtsbeitrag psychologische Mechanismen, die bei der Entstehung, Aufrechterhaltung und Therapie viszeraler Schmerzen wichtig sind. Dabei liegt der Fokus auf positiven und negativen Erwartungseffekten im psychosozialen Behandlungskontext. Therapieerwartungen können Krankheitssymptome sowohl positiv als auch negativ beeinflussen. Diese gemeinhin als Placebo- und Noceboeffekte bekannten Phänomene, die durch die Arzt-Patient Kommunikation, Lernprozesse, Stress und Furcht vermittelt werden, sind auch für den Viszeralschmerz bei gastrointestinalen Erkrankungen zunehmend anerkannt und Gegenstand aktueller grundlagenwissenschaftlicher und klinischer Forschungsaktivitäten. Neue interdisziplinäre und translationale Forschungsansätze aus der Forschung zu Placebo- und Noceboeffekten liefern spannende Einblicke in die zahlreichen Verbindungen und Wechselbeziehungen zwischen Darm und Gehirn bei normalen wie auch pathologischen Darm-Hirn Interaktionen und können dazu beitragen, die Pathophysiologie von Erkrankungen, die mit viszeralen Schmerzen einhergehen, besser zu verstehen und wichtige Erkenntnisse für neue Therapieansätze zu gewinnen.

Abstract

The experience of pain is shaped by a multitude of biological, psychological and social factors and is thus a complex psychological experience to be distinguished from nociception. Accordingly, the experience of pain can be modulated by psychological factors, and chronic pain conditions constitute biopsychosocial disorders. This is also true for visceral pain, which involves specific psychophysiological principles and neurobiological mechanisms, calling for an interdisciplinary approach at the interface of gastroenterology, psychology, pain research and the neurosciences. Based on the bidirectional connections between the gut and the brain and building on a biopsychosocial model, this review article describes psychological mechanisms that are important in the development, maintenance, and treatment of visceral pain. The focus is on positive and negative expectancy effects within the psychosocial treatment context. Treatment expectations can influence symptoms of the gut-brain axis, especially visceral pain, both positively and negatively. These phenomena, commonly known as placebo and nocebo effects, are mediated by doctor-patient communication, learning processes, stress, and fear. New interdisciplinary and translational research approaches from research on placebo and nocebo effects provide exciting insights into normal and pathological gut-brain interactions and may improve our knowledge about the etiology and pathophysiology of visceral hyperalgesia and interoceptive hypervigilance and provide important insights into new therapeutic approaches.



Publication History

Received: 22 June 2022

Accepted: 20 October 2022

Article published online:
16 February 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Aziz Q, Giamberardino MA, Barke A. et al. The IASP classification of chronic pain for ICD-11: chronic secondary visceral pain. Pain 2019; 160: 69-76
  • 2 Engel GL.. The need for a new medical model: a challenge for biomedicine. Science 1977; 196: 129-136
  • 3 Fava GA, Sonino N.. From the Lesson of George Engel to Current Knowledge: The Biopsychosocial Model 40 Years Later. Psychother Psychosom 2017; 86: 257-259
  • 4 Treede RD.. The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes. Pain Rep 2018; 3: e643
  • 5 Elsenbruch S, Icenhour A, Enck P.. Viszeraler Schmerz – eine biopsychologische Perspektive. e-Neuroforum 2017; 23: 141-148 doi:
  • 6 Furness JB.. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 2012; 9: 286-294
  • 7 Breit S, Kupferberg A, Rogler G. et al. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry 2018; 9: 44
  • 8 Agirman G, Yu KB, Hsiao EY.. Signaling inflammation across the gut-brain axis. Science 2021; 374: 1087-1092
  • 9 Gribble FM, Reimann F.. Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium. Annu Rev Physiol 2016; 78: 277-299
  • 10 Cryan JF, O'Riordan KJ, Cowan CSM. et al. The Microbiota-Gut-Brain Axis. Physiol Rev 2019; 99: 1877-2013
  • 11 Ran C, Boettcher JC, Kaye JA. et al. A brainstem map for visceral sensations. Nature 2022; 609: 320-326
  • 12 Labanski A, Langhorst J, Engler H. et al. Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology 2020; 111: 104501
  • 13 Cervero F.. Visceral versus somatic pain: similarities and differences. Dig Dis 2009; 27 Suppl 1 3-10
  • 14 Dunckley P, Wise RG, Aziz Q. et al. Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness. Neuroscience 2005; 133: 533-542
  • 15 Strigo IA, Duncan GH, Boivin M. et al. Differentiation of visceral and cutaneous pain in the human brain. J Neurophysiol 2003; 89: 3294-3303
  • 16 Koenen LR, Icenhour A, Forkmann K. et al. Greater fear of visceral pain contributes to differences between visceral and somatic pain in healthy women. Pain 2017; 158: 1599-1608
  • 17 Vlaeyen JWS, Crombez G, Linton SJ.. The fear-avoidance model of pain. Pain 2016; 157: 1588-1589
  • 18 Meulders A.. Fear in the context of pain: Lessons learned from 100 years of fear conditioning research. Behav Res Ther 2020; 131: 103635
  • 19 Verne GN, Himes NC, Robinson ME. et al. Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain 2003; 103: 99-110
  • 20 Elsenbruch S, Enck P.. Placebo effects and their determinants in gastrointestinal disorders. Nature Reviews Gastroenterology & Hepatology 2015; 12: 472-485
  • 21 Koenen LR, Pawlik RJ, Icenhour A. et al. Associative learning and extinction of conditioned threat predictors across sensory modalities. Commun Biol 2021; 4: 553
  • 22 Van Oudenhove L, Kragel PA, Dupont P. et al. Common and distinct neural representations of aversive somatic and visceral stimulation in healthy individuals. Nat Commun 2020; 11: 5939
  • 23 Icenhour A, Petrakova L, Hazzan N. et al. When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm. Neuroimage 2021; 238: 118229
  • 24 Kleine-Borgmann J, Schmidt K, Scharmach K. et al. Does pain modality play a role in the interruptive function of acute visceral compared with somatic pain?. Pain 2021;
  • 25 Keefer L, Ballou SK, Drossman DA. et al. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology 2022; 162: 300-315
  • 26 Frieling T, Schemann M, Enck P.. Neurogastroenterologie. De Gruyter 2017; doi:
  • 27 Elsenbruch S, Häuser W, Jänig W.. Viszeraler Schmerz. Schmerz 2015; 29: 496-502
  • 28 Layer P, Andresen V, Allescher H. et al. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. Z Gastroenterol 2021; 59: 1323-1415
  • 29 Drossman DA, Hasler WL., Rome IV-Functional GI. Disorders: Disorders of Gut-Brain Interaction. Gastroenterology 2016; 150: 1257-1261
  • 30 Aulenkamp J, Steinmüller K, Icenhour A. et al. Vom Bauchgefühl zum viszeralen Schmerz. Der Schmerz 2021;
  • 31 Enck P, Chae Y, Elsenbruch S.. Novel designs and paradigms to study the placebo response in gastroenterology. Curr Opin Pharmacol 2017; 37: 72-79
  • 32 Elsenbruch S, Labrenz F.. Nocebo Effects and Experimental Models in Visceral Pain. Int Rev Neurobiol 2018; 138: 285-306
  • 33 Vase L, Robinson ME, Verne GN. et al. The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients. An empirical investigation. Pain 2003; 105: 17-25
  • 34 Price DD, Craggs J, Verne GN. et al. Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 2007; 127: 63-72
  • 35 Lu HC, Hsieh JC, Lu CL. et al. Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: a 3T-fMRI study. Pain 2010; 148: 75-83
  • 36 Schmid J, Theysohn N, Ga F. et al. Neural mechanisms mediating positive and negative treatment expectations in visceral pain: a functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers. Pain 2013; 154: 2372-2380
  • 37 Elsenbruch S, Kotsis V, Benson S. et al. Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders. Pain 2012; 153: 382-390
  • 38 Elsenbruch S, Schmid J, Bäsler M. et al. How positive and negative expectations shape the experience of visceral pain: an experimental pilot study in healthy women. Neurogastroenterol Motil 2012; 24: 914-e460
  • 39 Lieberman MD, Jarcho JM, Berman S. et al. The neural correlates of placebo effects: a disruption account. Neuroimage 2004; 22: 447-455
  • 40 Schmid J, Langhorst J, Gaß F. et al. Placebo analgesia in patients with functional and organic abdominal pain: a fMRI study in IBS, UC and healthy volunteers. Gut 2015; 64: 418-427
  • 41 Lee HF, Hsieh JC, Lu CL. et al. Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients. Pain 2012; 153: 1301-1310
  • 42 Elsenbruch S, Rosenberger C, Bingel U. et al. Patients with irritable bowel syndrome have altered emotional modulation of neural responses to visceral stimuli. Gastroenterology 2010; 139: 1310-1319
  • 43 Kaptchuk TJ, Friedlander E, Kelley JM. et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One 2010; 5: e15591
  • 44 Lembo A, Kelley JM, Nee J. et al. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain 2021; 162: 2428-2435
  • 45 Bingel U, Wanigasekera V, Wiech K. et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Science translational medicine 2011; 3: 70ra14-70ra14
  • 46 Bingel U.. Avoiding nocebo effects to optimize treatment outcome. Jama 2014; 312: 693-694
  • 47 Colloca L, Miller FG.. The nocebo effect and its relevance for clinical practice. Psychosom Med 2011; 73: 598-603
  • 48 Mahr A, Golmard C, Pham E. et al. Types, frequencies, and burden of nonspecific adverse events of drugs: Analysis of randomized placebo-controlled clinical trials. Pharmacoepidemiology and drug safety 2017; 26: 731-741
  • 49 Pan PH, Tonidandel AM, Aschenbrenner CA. et al. Predicting acute pain after cesarean delivery using three simple questions. Anesthesiology 2013; 118: 1170-1179
  • 50 Blichfeldt-Eckhardt MR, Ording H, Andersen C. et al. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy. Pain 2014; 155: 2400-2407
  • 51 Peerdeman KJ, van Laarhoven AIM, Keij SM. et al. Relieving patients' pain with expectation interventions: a meta-analysis. Pain 2016; 157: 1179-1191
  • 52 Schmid J, Bingel U, Ritter C. et al. Neural underpinnings of nocebo hyperalgesia in visceral pain: A fMRI study in healthy volunteers. Neuroimage 2015; 120: 114-122
  • 53 Craig AD.. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 2003; 13: 500-505
  • 54 Linnman C, Rougemont-Bücking A, Beucke JC. et al. Unconditioned responses and functional fear networks in human classical conditioning. Behav Brain Res 2011; 221: 237-245
  • 55 Au Yeung ST, Colagiuri B, Lovibond PF. et al. Partial reinforcement, extinction, and placebo analgesia. Pain 2014; 155: 1110-1117
  • 56 Hunter T, Siess F, Colloca L.. Socially induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation. Eur J Pain 2014; 18: 914-922
  • 57 Swider K, Bąbel P.. The effect of the sex of a model on nocebo hyperalgesia induced by social observational learning. Pain 2013; 154: 1312-1317
  • 58 Vögtle E, Barke A, Kröner-Herwig B.. Nocebo hyperalgesia induced by social observational learning. Pain 2013; 154: 1427-1433
  • 59 Jozefowiez J.. Associative Learning. In: Seel NM, Hrsg. Encyclopedia of the Sciences of Learning. Boston, MA: Springer US; 2012: 330-334
  • 60 Labus JS, Hubbard CS, Bueller J. et al. Impaired emotional learning and involvement of the corticotropin-releasing factor signaling system in patients with irritable bowel syndrome. Gastroenterology 2013; 145: 1253-1261 e1251-1253
  • 61 Icenhour A, Langhorst J, Benson S. et al. Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome. Neurogastroenterol Motil 2015; 27: 114-127
  • 62 Forkmann K, Wiech K, Ritter C. et al. Pain-specific modulation of hippocampal activity and functional connectivity during visual encoding. J Neurosci 2013; 33: 2571-2581
  • 63 Forkmann K, Wiech K, Sommer T. et al. Reinstatement of pain-related brain activation during the recognition of neutral images previously paired with nociceptive stimuli. Pain 2015; 156: 1501-1510
  • 64 Koenen LR, Icenhour A, Forkmann K. et al. From Anticipation to the Experience of Pain: The Importance of Visceral Versus Somatic Pain Modality in Neural and Behavioral Responses to Pain-Predictive Cues. Psychosom Med 2018; 80: 826-835
  • 65 Moreira MF, Gamboa OL, Pinho Oliveira MA.. A single-blind, randomized, pilot study of a brief mindfulness-based intervention for the endometriosis-related pain management. Eur J Pain 2022; 26: 1147-1162
  • 66 Botella C, Fernández-Álvarez J, Guillén V. et al. Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review. Curr Psychiatry Rep 2017; 19: 42
  • 67 McLean CP, Foa EB.. Emotions and emotion regulation in posttraumatic stress disorder. Curr Opin Psychol 2017; 14: 72-77
  • 68 Keefer L, Bedell A, Norton C. et al. How Should Pain, Fatigue, and Emotional Wellness Be Incorporated Into Treatment Goals for Optimal Management of Inflammatory Bowel Disease?. Gastroenterology 2022; 162: 1439-1451
  • 69 Kawanishi H, Sekiguchi A, Funaba M. et al. Cognitive behavioral therapy with interoceptive exposure and complementary video materials for irritable bowel syndrome (IBS): protocol for a multicenter randomized controlled trial in Japan. Biopsychosoc Med 2019; 13: 14