270 inconsistent, mixed information and experiences in the clinical setting. Studies indicate that the amygdala is directly involved in coding not only fear but also ambiguity and uncertainty, and amygdala reactivity has previously been linked to classical conditioning under uncertain conditions 49. Moreover, what we observed in our chapter 2 metaanalysis was that, when compared to meta-analyses on placebo effects, learned effect on pain that rely on negative rather than positive associations appear to be larger in magnitude –albeit we were not able to systematically compare nocebo and placebo effects in the same set of studies. A potential stronger potency of negative, as compared to positive associations may in part be explained by enhanced learning under negative conditions, such as in experiments where participants learn to expect pain worsening rather than pain relief. We thus observe that during negative pain experiences a potent process of associative learning may interact with fear processing subcortically in the limbic system to create negative expectations and exert an important and enduring effect of the brain and its processing of pain. Increased negativity: the role of fear A long line of research has indicated that negative emotions, experiences, and negatively framed information are given more importance and learned more firmly by the brain 50–54, something thought to have an evolutionary explanation in the significance of negative information in avoiding threat 55. In line with earlier work on fear 3,50,55, our experiment in chapter 5 indicated that during conditioning, fear resulting from intense pain experiences adds to negative learning, but when the higher pain is never experienced but only anticipated, learning remains mostly unaffected. Chapter 5 thus in part suggests that a concrete negative experience such as increased pain leads to worse pain responses than a mere anticipated negative experience,
RkJQdWJsaXNoZXIy MTk4NDMw