RSD/CRPS: the end of the beginning.

The history of medicine provides perspective invisible from PubMed. Past theories and practices seem risible until one considers which moderns medical ''facts " will amuse future generations. Neurological disorders have been particularly difficult to resolve since anatomy and function are so complex. Primitive societies blamed the gods for seizures and strokes. Disease causality was eventually internalized, but localization of neural function and dysfunction remained poor for centuries, wandering through the uterus (hysteria) and heart (emotions) among other organs en route to the nervous system. Then, during the mid-20th century Freudian era, neurological disorders without visible localizing lesions (including movement disorders , autism, and schizophrenia) were often attributed to neurotic reactions to psychological traumas rather than to disease. Imperfect mothers figured prominently. These dead-end theories still circulate in some cultures, but have faded in western medicine as identification of cellular and molecular underpinnings of neurological conditions map the path towards diagnosis and cure. We are witnessing such a transition in the complex regional pain syndrome (CRPS). CRPS certainly seemed suspicious. How could a minor or healed limb injury cause pain, swelling, abnormal color and temperature, disordered sweating and movement , for months or even years? And the sex ratio among patients (consistently P 75% women) furthered suspicions of hysteria or neurosis in physicians (consistently P 75% men). In the 1990s Dutch surgeon/scien-tist, R.J.A. Goris and his coworkers pioneered modern study of CRPS-I, the subtype then thought not to involve nerve injury. In addition to large-scale phenotyp-ing [17], they identified the first evidence of nerve injuries [16] and conducted controlled treatment trials [11] among other achievements. Further support for biological causality came from discovering high levels of pro-inflammatory cytokines in skin, cerebrospinal fluid, and blood of CRPS-I patients [2,6,15], and identification of microcirculatory abnormalities including hypoxia and endothelial dysfunction [8,13]. Confirmation of chronic focal axonal injuries in CRPS-I [1,10] united the CRPS-I and II subtypes. Twenty-first century electronic medical charts now permit data-mining from larger and more representative populations then can be recruited from pain-clinics, although this approach is still limited by definitional and diagnostic vagueness. The first such study [12] reminded us that most CRPS-I patients recover – a welcome antidote to pervasive pessimism. Recovery can also be inferred from the fact that CRPS prevalence peaks in midlife, rather than continually increasing with age as would be expected for a lifelong , non-fatal condition. The 2nd study used detailed diagnoses by …