Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: An fMRI study in healthy placebo responders and nonresponders

• Published in: Pain (Amsterdam) Vol. 153; no. 2; pp. 382 - 390
• Main Authors: Elsenbruch, Sigrid, Kotsis, Vassilios, Benson, Sven, Rosenberger, Christina, Reidick, Daniel, Schedlowski, Manfred, Bingel, Ulrike, Theysohn, Nina, Forsting, Michael, Gizewski, Elke R.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.02.2012; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Adolescent; Adult; Analgesia - methods; Analgesia - psychology; Analgesics; Attitude to Health; Biological and medical sciences; Female; fMRI; Fundamental and applied biological sciences. Psychology; Humans; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - standards; Male; Medical sciences; Middle Aged; Neuropharmacology; Nocebo effect; Pain Measurement - methods; Pharmacology. Drug treatments; Placebo analgesia; Placebo Effect; Rectal distension; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; Visceral pain; Visceral Pain - physiopathology; Visceral Pain - psychology; Visceral Pain - therapy; Young Adult; Rectal distension; fMRI; Nocebo effect; Visceral pain; Placebo analgesia; Oxygen; Central nervous system; Probability; Nuclear magnetic resonance imaging; Encephalon; Analgesia; Somatosensory cortex; Analgesic; Pain; Somesthetic pathway; Placebo; Thalamus; Models; Expectation; Functional imaging
• ISSN: 0304-3959; 1872-6623; 1872-6623
• DOI: 10.1016/j.pain.2011.10.036

In this placebo analgesia study, the expectation of pain relief reduced perceived painfulness of visceral stimuli, which was associated with activity changes in thalamus, and prefrontal and somatosensory cortices. This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N = 36 healthy subjects, the blood oxygen level–dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0% > 100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.