Learning pain-related fear: Neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain

• Published in: Neurobiology of learning and memory 2014-12, Vol.116, p.36-45
• Main Authors: Gramsch, Carolin, Kattoor, Joswin, Icenhour, Adriane, Forsting, Michael, Schedlowski, Manfred, Gizewski, Elke R., Elsenbruch, Sigrid
• Format: Article
• Language: English
• Subjects: Adult; Behavioral psychophysiology; Biological and medical sciences; Brain - physiopathology; Brain Mapping; Conditioning, Classical - physiology; Extinction; Extinction, Psychological - physiology; Fear & phobias; Fear - physiology; Fear - psychology; Fear conditioning; Female; Functional magnetic resonance imaging; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Image Processing, Computer-Assisted; Irritable bowel syndrome; Magnetic Resonance Imaging; Male; Medical sciences; Memory; Neurobiology; Neurons - physiology; Other diseases. Semiology; Pain; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Reinstatement; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Visceral pain; Visceral Pain - physiopathology; Visceral Pain - psychology; Young Adult
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2014.08.003

•We assessed rapid associative learning and memory of abdominal pain-related fear.•Abdominal pain stimuli are effective unconditioned stimuli.•Learning occurs rapidly without full contingency awareness.•Neural structures include the insula, somatosensory cortex, putamen and cingulate cortex.•Results have implications for chronic abdominal pain. There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS–US learning trials (“rapid conditioning”), and explored the underlying neural substrates of these learning and memory processes. In N=24 healthy men and women, “rapid” fear acquisition was accomplished by pairing visual conditioned stimuli (CS+) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS−) were presented without US (differential delay conditioning with five CS+ and five CS− presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS–US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p