180 nocebo responses. Importantly, nocebo magnitudes across all groups correlated with reported fear during conditioning. These findings bear a number of implications related to both experimental models and clinical practices. The finding that higher pain levels produced larger nocebo responses and that this was mediated by fear may be linked to previous fear studies 20,22,23,48. Fear is a response that can be relatively impenetrable to cognitive control 24 and can be learned via classical conditioning 49,50. Just like nocebo conditioning models, fear-avoidance models consider pain-related fear to be a key factor in certain types of chronic pain 20. Notably, Crombez and colleagues 48 studied a sample of chronic back pain patients and found that pain-related fear may be even more disabling than pain itself. In the current study we show that, during conditioning, fear in response to the experience of high pain may have a direct amplifying effect on the acquisition of nocebo responses. This finding may be a novel link between fear of pain and nocebo hyperalgesia, as both are postulated to play a role in pain conditions 20,51. Studying fear in relation to the extinction of nocebo hyperalgesia may also provide insights into pain chronification. Nocebo hyperalgesia is sometimes found to be resistant to extinction 27,52,53. In the present study, nocebo responses were extinguished in the Control group but in the High-pain group they remained statistically significant. As the extinction rate of nocebo responses was not hindered by higher pain stimulations, it is apparent that in the High-pain group the substantially larger induced effects led to residual nocebo responses. It is therefore reasonable to expect that, after a longer extinction phase, nocebo responses would eventually be extinguished even following higher pain stimulations. Nevertheless, high pain leading to residual nocebo responses bears important implications. In clinical terms this effect may indicate that, compared to lower pain, higher pain not only produces
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