Complex regional pain syndrome: more than a peripheral disease

SUMMARY At early stages, complex regional pain syndrome (CRPS) is clinically characterized by damage of peripheral tissues and nerves (edema, activation of osteoblasts, hyperalgesia to blunt pressure). These signs are the result of a dysbalance of pro- and anti-inflammatory cytokines, which normalizes approximately 6 months after the beginning of the disease, independent from clinical outcome. At the same time, evolving clinical signs such as allodynia, cold hyperalgesia, reduced tactile acuity or symptoms of disrupted body representation (e.g., neglect-like syndrome, impaired hand laterality recognition or shift of the body midline) suggest a crucial role of the CNS in the pathophysiology of this pain syndrome. Imaging studies have found a severe but reversible reduction of the cortical hand representation (primary and secondary somatosensory cortices and primary motor cortices). Interestingly however, complex multisensory integration in central association areas are unaffected in CRPS, as patients are capable of integrating artificial body parts or recognize 2D forms despite tactile dysfunction. Furthermore, despite its unilateral clinical manifestation, it has been shown that in CRPS but not in other unilateral neuropathic pain syndromes, alterations in cortical excitability occur bilaterally, both in sensory and motor regions. In conclusion, a more widespread and bilateral pattern of CNS reorganization appears to characterize CRPS, which might be related to dysfunctions in the basal ganglia or in thalamo-cortical structures. Consequently, CRPS treatment should involve not only anti-inflammatory measures and pain therapy, but also the integration of neurorehabilitative training programs.