Background and Aim. Behavioural studies have demonstrated aberrant safety-processing in fibromyalgia (FM), and suggested that patients accumulate new potential pain-related threats more effectively than extinguishing old threats that are not as painful or threatening anymore. The aim of the current study was to investigate the neural correlates of conditioned pain responses and its relationship to emotional distress in FM (n=67) and healthy controls (HC,n=34).
 
Method. Using functional magnetic resonance imaging (fMRI), we tracked conditioned pain responses to an identical mid-painful pressure (P3) depending on whether it was following a green (P3green) or red (P3red) cue, that was previously associated with low or high painful pressure stimuli, respectively. The subjects rated pain intensity following each stimulus.
 
Results. FM displayed increased P3green ratings over time, while P3red ratings remained elevated. HC adapted all pain ratings to resemble medium pain. FM exhibited increased activation for [P3green>P3red] in M1/aIns, whereas HC showed increased S2/aIns response to [P3red>P3green]. High pain catastrophizing ratings (PCS) in FM co-varied with heightened brain activation for [P3green] in dlPFC (p(FWE)=0.021,t=4.56) and vmPFC/OFC (p(FWE)<0.001,t=4.34); and [P3green>P3red] in dACC/MCC (p(FWE)=0.003,t=5.10), superior temporal pole extending to aIns(p(FWE)=0.007,t=4.85), bilateral thalamus (p(FWE)<0.001,t=4.63), and pIns(p(FWE)=0.001,t=4.56). Psycho-physiological connectivity for FM[P3green>P3red]*PCS revealed a significant negative interaction between thalamus and bilateral inferior parietal lobe.
 
Conclusion. In alignment with behavioural studies, the current data suggest that FM prioritize updating their cerebral representation to forming new potential pain-related associations rather than extinguishing old, less painful ones. Increased response to pain-related threat in FM may contribute to dysfunctional pain-protective behaviours and disability.

INCREASED NEURAL ACTIVATION FOR CONDITIONED PAIN RESPONSES FOLLOWING A FALSE LOW- VS HIGH PAIN CUE IS RELATED TO PAIN CATASTROPHIZING IN FIBROMYALGIA PATIENTS