Are the complex regional pain syndromes due to neurogenic inflammation?

Complex regional pain syndromes (CRPS) types I and II (formerly RSD [I] and causalgia [II]) nearly always follow some sort of trauma, and frequently a seemingly minor one such as an ankle sprain. Their clinical presentations are identical, but in type II there is a clinically verified nerve injury. For both types, the early stage presents with pain (both spontaneous and stimulus-evoked); edema; abnormal vasomotor, sudomotor, and (sometimes) pilomotor function; hypertrophy of hair and nail growth; and motor dysfunction characterized by weakness, tremor, or dystonia. This clinical picture is similar to the classic post-injury inflammatory phenomena—rubor, calor, dolor, tumor, and functio laesa. It is thus natural to ask whether RSD and causalgia are pathologic expressions of the normal responses to injury. The sensory innervation of a tissue contributes importantly to the classic signs of inflammation. For example, primary afferent nociceptor sensitization contributes to dolor, and the release of the primary afferent neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), play a major role in edema and vasodilatation (thus, tumor, rubor, and calor). The original hypothesis, attributed to Sudeck,1 linking CRPS and inflammation invoked “inflammation” in its then current and now most general sense. Modern versions of the hypothesis (e.g., references 2-5⇓⇓⇓) emphasize the possibility of an abnormality of the neural contribution to inflammation or “neurogenic” inflammation. In this issue of Neurology , Birklein et …