Complex regional pain syndrome (CRPS) is a chronic pain condition that usually arises from an injury or as a complication from a surgical procedure. CRPS can result from multiple mechanisms including active processes involving both the peripheral and the central nervous system and sickness like responses involving interactions between the immune and nervous systems. In animal models both peripheral and central sensitization as well as loss of inhibition has been implicated in neuropathic pain states. Glial cells, in particular microglia and astrocytes, are the immunocompetent cells in the central nervous system and are activated following tissue injury or inflammation. In animal studies, activated glia have been shown to be both necessary and sufficient for enhanced nociception. Using immunohistochemical techniques, this study evaluated the degree of astrocytic and microglial activation as well as neuronal loss in autopsy tissue from the cervical, thoracic and lumbar spinal cord of a patient afflicted with CRPS as compared to four control individuals. The major findings of this study are that in long standing CRPS there was significant posterior horn cell loss and activation of both microglia and astrocytes most prominently at the level of the original injury but extending throughout the entire length of the spinal cord. Our hope is that the data obtained from this and other studies of autopsy material may aid in elucidating the mechanisms involved in the pathophysiology of CRPS, which may lead to the refinement of current therapies as well as novel treatments.