Chapter 3 – Comprehensive review 87 show that nocebo responses also implicate other cognitive as well as affective processes, as evident by the involvement of areas such as the OFC and DLPFC, ACC, insula, amygdala, and hippocampus 18,19,59. Interestingly, studies that only employed conditioning but did not use negative suggestions to induce negative treatment expectations, did not observe an involvement of brain areas responsible for affective processes such as fear 57,58. Functional imaging in visceral models Two studies investigated negative treatment expectations in an experimental model of visceral pain in which a pressure-controlled barostat system was used to inflated rectal balloons to an individualized designated pressure. Two studies used verbal suggestions and 1 used conditioning methods alone to induce nocebo effects. Schmid and colleagues (2013) told participants that they would experience increased pain as a result of receiving an opioid antagonist in one scanning session and saline solution in a control session. In reality, only saline was administered intravenously. Participants reported significantly higher pain levels during the expectation of a hyperalgesic treatment, as compared to the control sessions. The fMRI analyses indicated significantly increased pain-induced activation within the somatosensory cortex under nocebo conditions. Moreover, negative expectations in the nocebo group led to increased insula activation compared to neutral expectations. In an fMRI study by this research group, Schmid and colleagues (2015) informed participants in a nocebo group that increased pain would occur over time due to sensitization, in response to repeated rectal distensions, while a control group did not receive any negative suggestions. In reality, previous work has revealed no evidence of sensitization 68. The nocebo group reported higher pain levels in the evocation phase as compared to
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