Mechanisms of Emotional-motivational Pain Processing in Health and Disease

The experience of pain is more than the conscious perception of nociceptive signals. Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation for avoidance. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain responses. Such a negative hedonic shift is, for example, mirrored in very high comorbidity rates of chronic pain and affective disorders such as depression and anxiety. However, appropriate psychophysical methods to differentiate sensory-discriminative and emotional-motivational pain processing in humans are lacking. Therefore, only indirect evidence on the assumed negative hedonic shift in chronic pain is available, albeit understanding the mechanisms of such a shift would increase our knowledge on the development and maintenance of chronic pain in important ways with impact beyond pain research. The aim of this study is to develop methods that allow the differentiation of sensory-discriminative and emotional-motivational pain response and to characterize mechanisms of the negative hedonic shift.

A potential benefit of the study will be an increase in the knowledge on mechanisms of the development and maintenance of chronic pain with a focus on emotional-motivational processes likely also relevant in other diseases such as affective disorders.

This study involves only minimal risks for participants. The methods that will be used in the experimental investigations are within the range of standard procedures in pain research and experimental psychology and are frequently used in healthy participants and patients. Experimental pain stimulation will be adjusted to individual pain sensitivity, rendering the applied stimulation tolerable.

Substudy 1 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=31) will be recruited. The testing session will comprise a discrimination task and an avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task. Within the discrimination task, participants have to indicate whether they perceived a small increase in temperature or not. In the avoidance task, participants can avoid a painful stimulation by reacting fast enough to a visual cue. Participants will be randomly (balanced randomization) assigned to one of two learning conditions, either reinforcing successful discrimination or avoidance, to increase sensory-discriminative or emotional-motivational pain responses. Reinforcement, implemented by small monetary wins, will start depending on the condition after half the trials of the discrimination or the avoidance task. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires to investigate whether certain personality traits are related to learning capacity as tested in these tasks.

Substudy 2 Each participant will perform one testing session of approximately 1.5h duration at the Balgrist Campus, Balgrist University Hospital, Zurich. The sample will consist of patients with unspecific musculoskeletal chronic pain (N=31) and age- and sex-matched healthy controls (N=31). As in Substudy 1, the testing session will comprise the discrimination task and the avoidance task to assess sensory-discriminative and emotional-motivational pain components independently of each other. The tasks will be performed in counterbalanced order. After obtaining written informed consent, participants' individual heat pain threshold and tolerance will be determined, based on which the stimulation intensity to be used in the discrimination and the avoidance task will be calculated. After this assessment, participants either perform the discrimination or the avoidance task as in Substudy 1. In contrast to Substudy 1, reinforcement in the avoidance task will be implemented to decrease emotional-motivational pain responses because it is assumed that patients show already increased emotional-motivational compared to sensory-discriminative pain processing. Subjective ratings of perceived pain intensity and unpleasantness will be assessed within both tasks as control variables to test whether increases in sensory-discriminative or emotional-motivational pain processing generalize to the subjective response channel. At the end of the testing session, participants will complete several questionnaires, to investigate whether certain personality traits are related to heightened emotional-motivational pain processing.