Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients

Abstract

Placebo analgesia is a psychosocial context effect that is rarely studied in visceral pain. Patients with irritable bowel syndrome (IBS) exhibit visceral hyperalgesia and heightened affective/cognitive brain region activation during visceral stimuli. Psychological factors alter the pain and brain activation pattern, and these changes are more pronounced in IBS patients. Expectation constitutes the major neuropsychological mechanism in the placebo effect. This study confirmed the heightened affective/cognitive brain responses in IBS patients during visceral placebo analgesia using a placebo model with expectation, which was enhanced by suggestion and conditioning. Seventeen IBS patients and 17 age-/sex-matched controls were enrolled. Psychophysical inventories (Hospital Anxiety and Depression Scale [HADS], visual analogue scale, and short-form McGill questionnaire) were completed. Brain activity during placebo intervention and anticipation was assessed in response to rectal distension using 3T-functional magnetic resonance imaging. Suggestion-/conditioning-enhanced placebo was used to convince controls/patients of the efficacy of a newly developed intravenous drug (saline, in actuality) for the relief of rectal distension-induced visceral pain. A comparable visceral placebo analgesia was observed in IBS patients and control subjects. IBS patients demonstrated a higher HADS-anxiety score, which was predictive of a weak placebo effect. Suggestion-/conditioning-enhanced placebo evoked more activity in affective/cognitive brain regions (insula, midcingulate cortex, and ventrolateral prefrontal cortex [VLPFC]) in IBS patients than in healthy controls. VLPFC was also more active during anticipation in IBS patients. In conclusion, IBS patients and control subjects achieved comparable placebo analgesia during experimentally induced rectal pain. The visceral placebo analgesia produced heightened activity in affective/cognitive brain regions in IBS patients.

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…In addition, in the "50% condition," the placebo-induced pain relief was more pronounced in those subjects who believed they were in the active-treatment group . A direct comparison in the placebo Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses response to visceral pain between IBS patients and healthy volunteers demonstrated similar placebo responses at the behavioral level (magnitude of placebo analgesia) but a more pronounced neural response in affective and cognitive brain regions (insula, cingulate cortex, prefrontal cortex), suggesting altered neural processing of placebo-induced changes in pain perception in IBS and in patients with ulcerative colitis in remission (Lee et al, 2012;Schmid et al, 2015).…”

The Increased Level of Depression and Anxiety in Irritable Bowel Syndrome Patients Compared with Healthy Controls: Systematic Review and Meta-analysis

“…[10][11][12][13][15][16][17][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] The baseline characteristics of included studies are shown in Table 1 22,29 Sphere score in 1 study, 24 and the Beck Anxiety Inventory (BAI) in 1 study. 30 …”

Placebo effects and their determinants in gastrointestinal disorders

“…At the same time, placebo-induced neural modulation during rectal pain differed in patients with IBS as compared with healthy controls, involving multiple brain regions. 93,94 Specifically, in the study by Schmid et al, 93 healthy individuals as well as patients with ulcerative colitis in remission showed reduced activation in pain-related brain areas during placebo analgesia, whereas no changes could be observed in patients with IBS. These differences in neural modulation were most impressive in the cingulate cortex.…”