title: Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.
abstract: BACKGROUND
  Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm.
  
  
  METHODS
  During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses.
  
  
  RESULTS
  Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement.
  
  
  CONCLUSIONS
  Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS.
authors.affiliation: Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Icenhour
authors.forename: J
authors.initials: J
authors.lastname: Langhorst
authors.forename: S
authors.initials: S
authors.lastname: Benson
authors.forename: M
authors.initials: M
authors.lastname: Schlamann
authors.forename: S
authors.initials: S
authors.lastname: Hampel
authors.forename: H
authors.initials: H
authors.lastname: Engler
authors.forename: M
authors.initials: M
authors.lastname: Forsting
authors.forename: S
authors.initials: S
authors.lastname: Elsenbruch
mesh_terms: D015746:Abdominal Pain / Q000523:psychology; D000328:Adult; D001007:Anxiety; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology; D004108:Dilatation, Pathologic; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000503:physiopathology* / Q000523:psychology*; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D012007:Rectum / Q000503:physiopathology
keywords: extinction; fear conditioning; irritable bowel syndrome; pain-related fear; reinstatement; visceral pain