Generalization gradients in cued and contextual pain-related fear: an experimental study in healthy participants

Increasing evidence supports the notion that pain-related fear plays a key role in the transition from acute to chronic pain. Recent experimental data show that associative learning processes are involved in the acquisition of pain-related fear. An intriguing yet underinvestigated question entails how spreading of pain-related fear in chronic pain occurs. In a voluntary movement paradigm in which one arm movement (CS+) was followed by a painful stimulus and another was not (CS-) in the predictable group and painful stimuli were delivered during the intertrial interval (context alone) in the unpredictable group, we tested generalization of fear to six novel generalization movements (GSs) with varying levels of similarity between the original CS+ movement and CS- movement. Healthy participants (N = 58) were randomly assigned to the predictable or unpredictable group. Fear was measured via verbal ratings and eyeblink startle responses. Results indicated that cued pain-related fear spreads selectively to novel movements that are proprioceptively more similar to the CS+ than to those similar to the CS- in the predictable group, but not in the unpredictable group. This is the first study to demonstrate a generalization gradient of cued pain-related fear. However, this effect was only present in the startle eyeblink responses, but not in the verbal ratings. Taken together, this paradigm represents a novel tool to scrutinize the largely understudied phenomenon of the spreading of fear and avoidance in patients with chronic musculoskeletal pain and mapping possible pathological differences in generalization gradients and the spreading of pain in patients as compared with healthy controls.