The lack of clear understanding of the pathophysiology of chronic pain could explain why we currently have only a few effective treatments. Understanding how pain relief is realised during placebo analgesia could help develop improved treatments for chronic pain. Here, we tested whether experimental placebo analgesia was associated with altered resting-state cortical activity in the alpha frequency band of the electroencephalogram (EEG). Alpha oscillations have been shown to be influenced by top-down processes, which are thought to underpin the placebo response.Seventy-three healthy volunteers, split into placebo or control groups, took part in a well-established experimental placebo procedure involving treatment with a sham analgesic cream. We recorded ongoing (resting) EEG activity before, during, and after the sham treatment.We show that resting alpha activity is modified by placebo analgesia. Post-treatment, alpha activity increased significantly in the placebo group only (p < 0.001). Source analysis suggested that this alpha activity might have been generated in medial components of the pain network, including dorsal anterior cingulate cortex, medial prefrontal cortex, and left insula.These changes are consistent with a cognitive state of pain expectancy, a key driver of the placebo analgesic response. The manipulation of alpha activity may therefore present an exciting avenue for the development of treatments that directly alter endogenous processes to better control pain.

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