A new generation of war wounded veterans are now being seen in the VA Health Care System with blast injury induced traumatic injuries to the limbs. Dr. Kingery’s work relates to the potential to identify novel pharmacologic and clinical treatments for reducing pain and enhancing the quality of life in war-wounded veterans. Correspondingly, Dr. Kingery’s research interests are translational and clinical tissue research in Complex Regional Pain Syndrome (CRPS). Population based studies indicate that distal limb fracture is the most common cause of CRPS and, in collaboration with Dr. David Clark, his laboratory has developed a tibia fracture model in the rat and mouse that closely resembles CRPS. Distal tibia fractured rats and mice treated with 3-4-weeks cast immobilization exhibit paw allodynia, unweighting, increased spinal Fos-immunoreactivity, increased hindpaw skin temperature, edema, increased spontaneous protein extravasation, facilitated neuropeptide signaling, regional periarticular bone loss, mast cell and keratinocyte proliferation, epidermal thickening, increased keratinocyte expression of TNF, IL-1, IL-6, and NGF inflammatory mediators in the affected skin, increased IgM deposition in the affected skin and nerves, and B cell dependent nociceptive sensitization. In collaboration with Dr. Frank Birklein and Peter Drummond, Dr. Kingery’s research team recently published a study examining bilateral skin punch biopsies from 55 CRPS patients that demonstrated unilateral mast cell and keratinocyte proliferation, epidermal thickening, and keratinocyte inflammatory cytokine expression (TNF, IL-6) in early (< 3 month duration) CRPS affected skin. This study also found that increased keratinocyte and mast cell proliferation gradually resolved over time, despite persistent pain symptoms. These results are consistent with skin blister fluid studies indicating a gradual resolution of cutaneous inflammatory mediator (IL-6, TNF) expression over time in CRPS affected skin. Dr. Kingery is currently investigating the role of autoimmunity in the CRPS fracture model and testing the effects of CRPS patient antibodies in fracture mice lacking B cells.