Chapter 8 – General discussion 277 These are important questions for the field of pain and nocebo research to address and bear in mind while building experimental nocebo models. Idealized and exploratory models are a crucial means for pain research to cope with systems that are as difficult to study in their full complexity as pain 84. But the shortcomings of experimental modeling need to be moved to the foreground if we are to attempt improving the ecological validity and representational powers of experimental nocebo research. For example, a consensus could be achieved between researchers and clinicians regarding which models best and most accurately represent nocebo hyperalgesia, and these models can provide a basis on which nocebo effects are researched, as is largely the case for example for animal models of schizophrenia 85,86. Another solution for the distance between experimental nocebo models and real-world pain phenomena could be to utilize validation and calibration techniques based on clinical knowledge. Models play an important role in science, as vehicles for learning about the phenomena observed in the world that are out of reach or intensely convoluted, such as chronic pain. Experimental models of nocebo effects allow for ‘surrogative reasoning’, a mode of scientific investigation in which features and outcomes of a system are examined by studying a model, rather than reality itself 87. But this type of model-based reasoning, with its limitations as discussed above, should be based on active evaluation and adaptation of models 88,89 if we are to best represent real phenomena in patient populations. Bach and colleagues have proposed a valuable method to assess face validity and the fit of an experimental model, called retrodictive validity since the aim is to ‘retroactively predict’ the experimentally induced value of a given biobehavioral attribute 80,90 such as a nocebo effect on pain. In experimental research on such attributes, hypothetical true scores can be influenced by experimental manipulations, and this allows us to apply metrological calibrations. Bach and colleagues propose that an influenced value representing the true score in such a calibration experiment can provide a retrodictive
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