{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:23:43Z","timestamp":1791973423189,"version":"4.3.4"},"reference-count":84,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,3,18]],"date-time":"2009-03-18T00:00:00Z","timestamp":1237334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurologist S. Weir Mitchell first described \u201ccausalgia\u201d following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post\u2010traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I [CRPS\u2010I]). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD\/CRPS\u2010I is a post\u2010traumatic neuralgia associated with distal degeneration of small\u2010diameter peripheral axons. Small\u2010fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features\u2014spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating\u2014are explicable by small\u2010fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroeffector actions. Indeed, small\u2010fiber\u2013predominant polyneuropathies cause CRPS\u2010like abnormalities, and pathological studies of nerves from chronic CRPS\u2010I patients confirm small\u2010fiber\u2013predominant pathology. Small distal nerve injuries in rodents reproduce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degeneration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Restoring the interest of neurologists in RSD\/CRPS should improve patient care and broaden our knowledge of small\u2010fiber functions. 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