Background Complex regional pain syndrome (CRPS) is a painful condition with ~50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. Methods We used a previously-characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n=8–20/group) observed in humans. Our central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. Results We demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, we found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain derived neurotrophic factor in specific brain regions. Conclusions Our findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

The time window construct describes when and how an earlier experience will be enduring. According to the construct, there is a limited period after an event occurs, or time window, in which a second event can retrieve and be integrated with the memory of the first event. The construct also holds that when the integration occurs later in the time window, its effects are more enduring. This study examined the time window construct for session spacing with 6- to 18-month-old human infants. Infants of all ages exhibited the retention benefit of two (integrated) sessions only when the second session occurred within the time window, but only 6-month-olds remembered longer when it occurred late in the time window. Combined with 3-month-olds' data, these findings document the generality and predictive validity of the time window construct throughout the infancy period with one modification: Integration late in the time window only benefits infants younger than 9 months.

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale. ß 2005 Wiley Periodicals, Inc. Dev Psychobiol 47: 43-54, 2005.

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