WHAT DID PAVLOV'S DOGS HEAR? Perceptual alterations through conditioning and their pathogenic potential in chronic pain

Pain in its acute form has been tremendously beneficial throughout evolution as it enabled organisms to prevent future damage. Yet, once evolved into a more chronic state its adaptive nature becomes superimposed by a wide range of negative sequelea that determine patients’ lives and burden societies. Although considerable efforts have advanced our conceptualization of pain, the dissociation between tissue damage and pain perception remains challenging to understand and treat in contemporary research and clinical practices. Throughout the past decades, insights into the complex malleability of pain by emotions and cognitions have grown. Especially, an impressive body of research has focused on pain-related fear and within its vein the acknowledgment of associative learning processes and their influence on behavior. However, the influence of these learning processes on various perceptual processes remains poorly understood. One potential reason for such limited understanding can be found in the dominant behavioral focus in both experimental and clinical pain conditioning research. It was this current gap in pain research that served as an inspirational foundation for my PhD, with the aim to investigate the pathogenic potential of fear-learning induced alterations in perceptual processes within the context of (chronic) pain. In this doctoral dissertation, we start with a brief general introduction into the concept of pain and its evolution throughout past decades, highlighting contributions of psycho-behavioral research in the field of chronic pain (chapter 1). Next, we present a theoretical model based on a review of previous work on the influence of associative learning on perceptual discrimination and the relationship between discrimination of bodily sensations and pain in chronic pain patients (chapter 2). The basic tenet of the model is that associative fear learning contributes to the development of chronic pain through (1) an impaired interoceptive and proprioceptive discrimination acuity, and (2) induction of a perceptual bias towards processing bodily sensations as more intense, aversive, or even painful. In the first three studies, variations of a fear learning paradigm with visceral sensations in healthy volunteers were used to explore the influence of fear learning on the perception and discrimination of bodily sensations. In a first study, fear learning was found to influence perception thresholds as well as to impair visceral discrimination (chapter 3). In a second study, fear learning was found to induce an a priori decision-making bias such that visceral sensations are perceived as more intense (chapter 4). The data from the third study are currently still being collected, but preliminary findings are described (chapter 5). Taken together, results from these first set of studies suggest that associative learning mechanisms might indeed contribute to visceral hypersensitivity and impair visceral discrimination, which may be relevant for symptom generation in functional gastrointestinal disorders. In chapters 6 and 7, the focus shifts from visceral to movement-related somatic perception as a model of musculoskeletal pain. In three studies perceptual decision-making about somatic sensations was assessed during the execution of pain-associated movements. In the fourth and fifth study, we failed to observed fear generalization across movements and hence its influence on somatic perceptual decision-making processes remains unclear (chapter 6). In the sixth study, the influence of pain unpredictability on somatic perceptual decision-making was explored and unpredictability was found to induce a decision-making bias to perceive somatic stimuli as more intense during execution of movements associated with unpredictable pain (chapter 7). Next, using the data from study 2, potential modulatory effects of perception on psychophysiological measures are illustrated (chapter 8). Based on this finding, we discus in the ninth chapter the potential implications that fear learning-induced perceptual alterations pose for generalization research given its close relation to fear learning. In the final part, a general discussion is presented where the executed work is interpreted and integrated into previous research and the proposed model (chapter 10). At the end, final conclusions based on the conducted research are presented together with potential (clinical) implications, current limitations and future research plans.status: publishe