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 Nov;154(11):2372-2380. doi: 10.1016/j.pain.2013.07.013. Epub 2013 Jul 16.


To elucidate placebo and nocebo effects in visceral pain, we conducted a functional magnetic resonance imaging (fMRI) study to analyze effects of positive and negative treatment expectations in a rectal pain model. In 36 healthy volunteers, painful rectal distensions were delivered after intravenous application of an inert substance combined with either positive instructions of pain relief (placebo group) or negative instructions of pain increase (nocebo group), each compared to neutral instructions. Neural activation during cued-pain anticipation and pain was analyzed along with expected and perceived pain intensity. Expected and perceived pain intensity were significantly increased in the nocebo group and significantly decreased in the placebo group. In the placebo group, positive expectations significantly reduced activation of the somatosensory cortex during anticipation and of the insula, somatosensory cortex, and amygdala during pain delivery when compared to neutral expectations. Within the nocebo group, negative expectations led to significantly increased insula activation during painful stimulation. Direct group contrasts during expectation modulation revealed significantly increased distension-induced activation within the somatosensory cortex in the nocebo group. In conclusion, the experience and neural processing of visceral pain can be increased or decreased by drug-specific expectations. This first brain imaging study on nocebo effects in visceral pain has implications for the pathophysiology and treatment of patients with chronic abdominal complaints such as irritable bowel syndrome.

Keywords: Expectations; Functional magnetic resonance imaging; Nocebo; Placebo; Rectal distension; Visceral pain.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / physiology
  • Adolescent
  • Adult
  • Anticipation, Psychological
  • Anxiety / metabolism
  • Anxiety / psychology
  • Brain / anatomy & histology
  • Brain / physiology
  • Cues
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Narcotic Antagonists / pharmacology
  • Nervous System Physiological Phenomena*
  • Pain Measurement
  • Parasympatholytics / pharmacology
  • Physical Stimulation
  • Rectum / physiology
  • Saliva / metabolism
  • Socioeconomic Factors
  • Surveys and Questionnaires
  • Visceral Pain / therapy*
  • Young Adult


  • Narcotic Antagonists
  • Parasympatholytics
  • Hydrocortisone