Learning mechanisms in pain chronification—teachings from placebo research

Denne beskriver hvordan placebo-forskning bidrar til forståelsen av overgangen fra akutt smerte til kronisk smerte. Mange interessante prinsipper å få med seg her. Bl.a. årsaken til at det ikke er mulig å kile seg selv.


Abstract: This review presents a general model for the understanding of pain, placebo, and chronification of pain in the framework of cognitive neuroscience. The concept of a computational cost-function underlying the functional imaging responses to placebo manipulations is put forward and demonstrated to be compatible with the placebo literature including data that demonstrate that placebo responses as seen on the behavioural level may be elicited on all levels of the neuroaxis. In the same vein, chronification of pain is discussed as a consequence of brain mechanisms for learning and expectation. Further studies are necessary on the reversal of chronic pain given the weak effects of treatment but also due to alarming findings that suggest morphological changes in the brain pain regulatory systems concurrent with the chronification process. The burden of chronic pain is devastating both on the individual level and society level and affects more than one-quarter of the world’s population. Women are greatly overrepresented in patients with chronic pain. Hence, both from a general standpoint and from reasons of health equity, it is of essence to advance research and care efforts. Success in these efforts will only be granted with better theoretical concepts of chronic pain mechanisms that maps into the framework of cognitive neuroscience.

The seminal article of Craig with the description of pain as a homoeostatic emotion12 moved the field away from the concept of a “searching for pain center” in the brain to a systems-oriented understanding. The experience of pain was put in a behavioural perspective and the dynamics of the preprogrammed complex emotional reactions to acute pain were explained in terms of a dynamic regulatory system. Just as in all other expressions of emotion, the homoeostasis model for understanding pain provides both a basis for a prolongation of the feeling state but also, at the same time, an effective measure of social communication to alert others of, eg, danger. In addition, such a mechanism also serves to raise empathic responses in the group. The understanding of pain as a homoeostatic emotion has also contributed to the understanding of affective comorbidity in different pain syndromes because the mechanisms of both lowered mood and anxiety are based on similar regulatory mechanisms.53

Increasingly, the view on the brain function as a machinery for predictions has gained support. We and others have pointed out that this also is an important principle in pain perception and regulation and especially for the subjective reporting of pain.

Predictions entail the ability to internally maintain models of the world and to constantly update those with sparse multisource bits of information, principles that have been well established in sensory-motor learning.52 In short, upon an execution of a movement, an efferent copy is made as to serve as an internal model for the coming sensory feedback. This minimises the need for further computations as only discrepancies between the inner model and the received sensory feedback is ground for corrective behaviour, whereas expected input may be blocked from entering the motor-planning system. This understanding also explains why it is impossible to tickle oneself.6

Also, Kurzweil’s suggestion for the construction of the cortical architecture satisfies the needs for a multilevel system in which Bayesian principles for model optimisation can be harboured.27 The Bayesian principles posit that all current information is related to prior beliefs (ie, predictions).

We have left the era when the debate focused on whether a placebo effect is real or not.46 When placebo is understood in the context of dynamic complexity, that debate becomes redundant. Any notion that placebo would be constantly present and thus remains constant over time is incorrect because placebo rests on the discrepancy between the inner representational model and the current information inflow. If such a discrepancy remains over time, the inner model will update, and with the diminishing computational difference, and the placebo effect will disappear with time.

The ultimate difference in such a comparison system is of course if the expectation is no input but instead a sensory input is evoked as a surprise. In such situations with low predictability, the subjective experience of nociception seems to amplify.45

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