Pain reduction and enhancement can be produced by means of conditioning procedures, yet the role of awareness during the acquisition stage of classical conditioning is unknown. We used psychophysical measures to establish whether conditioned analgesic and hyperalgesic responses could be acquired by unseen (subliminally presented) stimuli. A 2 × 2 factorial design, including subliminal/supraliminal exposures of conditioning stimuli (CS) during acquisition/extinction, was used. Results showed significant analgesic and hyperalgesic responses (P < 0.001), and responses were independent of CS awareness, as subliminal/supraliminal cues during acquisition/extinction led to comparable outcomes. The effect was significantly larger for hyperalgesic than analgesic responses (P < 0.001). Results demonstrate that conscious awareness of the CS is not required during either acquisition or extinction of conditioned analgesia or hyperalgesia. Our results support the notion that nonconscious stimuli have a pervasive effect on human brain function and behavior and may affect learning of complex cognitive processes such as psychologically mediated analgesic and hyperalgesic responses.classical conditioning | awareness | consciousness | placebo | nocebo I t has been well established that pain can be altered by associative learning procedures (1-3). In the present study, we sought to establish whether conditioned analgesic and hyperalgesic responses could be acquired by unseen (subliminally presented) stimuli.The human brain can process sensory stimuli outside of conscious awareness (4), but it is not clear to what extent learning can take place when we are not aware of the associations being made. On one hand, associative learning with subliminally presented stimuli has been demonstrated [e.g., by Degonda and colleagues (5)]; on the other hand, a sizeable literature indicates that pain conditioning is mediated by conscious expectations (6-10). Studies of fear learning in humans suggest that emotional contingencies can be acquired nonconsciously, as demonstrated by conditioned changes in autonomic and motor responses (11)(12)(13)(14). In addition to evidence for conditioning of low-level physiological responses, a recent literature challenges the idea that nonconscious processing stops at an early perceptual level (4), suggesting that higher-order cognitive representations, such as meaning and goal pursuits, can be acquired nonconsciously (15). Moreover, findings from neuroimaging studies show that nonconscious stimuli have extensive representations in the human brain, activating a large number of cortical areas (16-18) at frequency bands previously seen as markers of conscious awareness (19). Taken together, these results suggest that nonconscious stimuli have a pervasive effect on human brain function and behavior and may affect learning of complex cognitive processes such as psychologically mediated pain responses.In a previous study, we found that consciously conditioned analgesic and hyperalgesic pain responses could be activate...