The impact of expectations
Perhaps you recognize the experience that taking a painkiller when you have a ferocious headache immediately decreases your pain, even if the drug cannot yet have influenced your physiology. There are many fundamental lab studies that show convincingly that our expectations have a powerful impact on our experiences. Telling people what to expect, for example how painful a specific stimulus will be, influences the pain that people actually experience, either for the better or for the worse. Also, influencing people’s expectations by repeatedly pairing two stimuli (e.g., pairing a specific drink with taking a painkiller) can lead to the previously neutral stimulus (the drink) triggering a similar response (pain relief) on its own, without the actual stimulus (painkiller) being present. This phenomenon, classical conditioning, is best known from Pavlov’s dogs. These learning mechanisms can induce both positive and negative expectations, resulting in positive (placebo) and negative (nocebo) effects.

Within our research group at the Health, Medical, and Neuropsychology Unit, we are conducting fundamental research into placebo and nocebo effects, subsidized by grants from the European Research Council and the Netherlands Organisation for Scientific Research awarded to Prof. Andrea Evers. In these studies, in which I have been actively involved from their conception, a large group of talented PhD-students are examining various combinations of learning mechanisms in search of the ideal way to influence physical symptoms, such as pain, itch, and fatigue. There is still much more to learn, for instance by examining how expectancy learning impacts our brain. We think, however, that our current state of knowledge can be put into practice, by looking into the applicability of these learning processes for patients.

The influence of expectations in patient populations
A number of fascinating studies on expectations have already been performed in patient groups. It has been shown, for instance, that the effectiveness of a painkiller after surgery is dramatically higher when patients are aware that they are being given the painkiller (open application) then when it is administered by a machine at an unknown time (hidden application). In another study, up to a year after ‘sham surgery’ on a meniscal tear, patients showed the same decrease in pain and the same increase in walking ability as patients who had actual surgery. When it comes to nocebo effects, a prominent example in clinical practice is the nausea that patients undergoing chemotherapy often experience already in response to a specific sight or odour (e.g., of the hospital). Moreover, telling patients that a certain procedure will be painful (which is standard practice) leads to the experience being perceived as more painful than if the pain is not explicitly mentioned. Thus, these studies clearly show the impact of expectations in clinical practice.

Expectations in patients with chronic pain
If you are a patient with, for instance, chronic pain symptoms, you will probably have had several learning experiences. Since there is no ‘gold standard’ treatment for chronic pain, most patients have negative experiences with unsuccessful treatments. Also, in order not to get patients’ hopes up too much, physicians may communicate that there is a high chance that a new treatment will not ‘work’. All of this information will lead to negative expectations that do not contribute to a successful symptom course or treatment outcome for patients. However, negative treatment experiences cannot be prevented, unfortunately, and it would be unethical for physicians to provide overly optimistic expectations regarding new treatment or not to inform patients about important potential side effects. With these dilemmas in mind, we are looking for ways to take account of and try to change these existing expectations in an ethical way. For example, research has shown that placebos are effective even when patients are informed about receiving a placebo, as long as the mechanisms behind its effects are explained (open-label placebo). Much more research is needed in this area to examine how we can optimally translate our lab-based knowledge to clinical practice.

Expectations as triggers and intervention opportunities in chronic pain
We are currently at the start of two major projects in patients with fibromyalgia (chronic widespread pain). In these projects, part of Andrea Evers’s VICI-grant, we will delve into the role of expectations for patients’ pain symptoms. The first project, conducted by Merve Karacaoglu, will examine whether the sensitivity to learning negative associations (nocebo conditioning) can predict pain progression over time. This sensitivity to nocebo effects will be examined by applying pressure pain stimuli that most closely resemble patients’ daily pain experiences. If this study finds that patients who are more sensitive to nocebo learning show more pain progression, this would enable us to identify patients at risk for symptom progression at an early stage. The second project, carried out by Simone Meijer, will examine the effectiveness of a new treatment method. The main idea is to attenuate previously learned negative associations related to pain. To do this, we will first condition participants so that they learn a connection between a placebo device and pain stimuli (nocebo conditioning). Subsequently, we will ‘overwrite’ (countercondition) this association by coupling the placebo device with low pain. By repeating this counterconditioning procedure over a number of weeks and by generalizing exercises to be carried out by the participants at home, we aim to decrease their pain symptoms in daily life. All of this will be performed in an open-label fashion, thus allowing actual implementation. These two studies will be an important step forward for our knowledge on the role of learning processes in patients with chronic somatic symptoms, and provide the potential to influence patients’ expectations by means of an intervention.