Julia Schmid1, Jost Langhorst2, Florian Gaß3, Nina Theysohn4, Sven Benson1, Harald Engler1, Elke R Gizewski5, Michael Forsting4, Sigrid Elsenbruch1. 1. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 2. Integrative Gastroenterology, Clinic for Internal and Integrative Medicine, Kliniken Essen-Mitte, Essen, Germany. 3. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany Integrative Gastroenterology, Clinic for Internal and Integrative Medicine, Kliniken Essen-Mitte, Essen, Germany. 4. Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 5. Clinic for Neuroradiology, Medical University Innsbruck, Innsbruck, Austria.
Abstract
OBJECTIVE: Understanding the neural circuitry of placebo analgesia in the context of visceral pain is increasingly important given evidence of clinical benefit of placebo treatment in IBS. This functional MRI study addressed placebo analgesia in IBS, UC and healthy control (HC) volunteers. DESIGN:Painful rectal distensions were delivered in N=17 patients with IBS , N=15 patients with UC in remission, and sex-matched and age-matched HCs in an adaptation phase followed by intravenous application ofsaline combined with either positive instructions of pain relief (placebo) or neutral instructions (control). Neural activation during cued-pain anticipation and pain was analysed along with ratings of expected and perceived pain and measures of negative affectivity and salivary cortisol concentrations. Correlational analyses between placebo analgesia responses and negative affect were accomplished. RESULTS: HC and UC revealed significant pain inhibition during placebo analgesia, as evidenced by reduced neural activation in pain-related brain areas. In contrast, patients with IBS failed to effectively engage neural downregulation of pain, as evidenced by the absence of placebo-induced changes in distension-induced brain activation, resulting in a significant group difference in the cingulate cortex compared with HC. Depression scores correlated with weaker placebo analgesia, whereas state and trait anxiety were not associated. CONCLUSIONS:Patients with IBS failed to effectively engage neural downregulation of rectal distension-induced pain during placebo analgesia, indicating a specific deficit in cognitive pain inhibition, which may in part be mediated by depression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
RCT Entities:
OBJECTIVE: Understanding the neural circuitry of placebo analgesia in the context of visceral pain is increasingly important given evidence of clinical benefit of placebo treatment in IBS. This functional MRI study addressed placebo analgesia in IBS, UC and healthy control (HC) volunteers. DESIGN: Painful rectal distensions were delivered in N=17 patients with IBS , N=15 patients with UC in remission, and sex-matched and age-matched HCs in an adaptation phase followed by intravenous application of saline combined with either positive instructions of pain relief (placebo) or neutral instructions (control). Neural activation during cued-pain anticipation and pain was analysed along with ratings of expected and perceived pain and measures of negative affectivity and salivary cortisol concentrations. Correlational analyses between placebo analgesia responses and negative affect were accomplished. RESULTS: HC and UC revealed significant pain inhibition during placebo analgesia, as evidenced by reduced neural activation in pain-related brain areas. In contrast, patients with IBS failed to effectively engage neural downregulation of pain, as evidenced by the absence of placebo-induced changes in distension-induced brain activation, resulting in a significant group difference in the cingulate cortex compared with HC. Depression scores correlated with weaker placebo analgesia, whereas state and trait anxiety were not associated. CONCLUSIONS:Patients with IBS failed to effectively engage neural downregulation of rectal distension-induced pain during placebo analgesia, indicating a specific deficit in cognitive pain inhibition, which may in part be mediated by depression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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