What is the pathophysiology of complex regional pain syndrome (CRPS)?

Updated: Nov 08, 2018
  • Author: Steven J Parrillo, DO, FACOEP, FACEP; Chief Editor: Andrew K Chang, MD, MS  more...
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No single hypothesis explains all features of reflex sympathetic dystrophy syndrome (RSDS). Schwartzman stated that a common mechanism may be injury to central or peripheral neural tissue. [2] Roberts proposed that sympathetic pain results from tonic activity in myelinated mechanoreceptor afferents. Input causes tonic firing in neurons that are part of a nociceptive pathway. Campbell et al propose a hypothesis that places the primary abnormality in the peripheral nervous system. [3] More recent articles agree that the cause is still unknown. [4] Recent interest has focused on an immune-mediated mechanism. [5]

Most authors now agree that complex regional pain syndrome (CRPS) is a neurologic disorder affecting central and peripheral nervous systems. [6, 7] Mechanisms include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. [7, 8]

Other etiologic possibilities have been suggested. German research has noted the association between elevated levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and enhanced tumor necrosis factor-alpha activity in patients with polyneuropathy with allodynia. [9] Other German researchers have described autoantibodies in patients with CRPS, especially CRPS type 2. [10]

Harvard researchers Oaklander and Fields have proposed that distal degeneration of small-diameter peripheral axons may be responsible for the pain, vasomotor instability, edema, osteopenia, and skin hypersensitivity of CRPS-1. [11]

The recent association between the use of ACE inhibitors and CRPS has caused some to consider a neuroinflammatory pathogenesis. [12]

Recent research has demonstrated cortical changes, suggesting a possible role in pathophysiology. [13]

All agree that, regardless of the mechanism, the patient experiences intense, burning pain in one or more extremities.

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