• Maral Tajerian, David Leu, Yani Zou, Peyman Sahbaie, Wenwu Li, Hamda Khan, Vivian Hsu, Wade Kingery, Ting Ting Huang, Lino Becerra, and J David Clark.
• From the Veterans Affairs Palo Alto Health Care System, Palo Alto, California (M.T., P.S., W.L., H.K., J.D.C.); Department of Anesthesiology, Stanford University School of Medicine, Stanford, California (M.T., P.S., W.L., J.D.C.); Palo Alto Institute of Research and Education, Palo Alto, California (M.T., D.L., Y.Z., H.K., V.H.); Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (Y.Z., T.T.H.); Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (W.K.); Geriatrics Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (D.L., Y.Z., V.H., T.T.H.); and P.A.I.N. Group, Departments of Anesthesia and Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts (L.B.).
• Anesthesiology. 2014 Oct 1; 121 (4): 852-65.

BackgroundComplex regional pain syndrome (CRPS) is a painful condition with approximately 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.MethodsThe authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The 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.ResultsThe authors 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, the authors 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.ConclusionsThe study 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.

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