Brain in complex regional pain syndrome

Research output: ThesisDoctoral ThesisCollection of Articles


Complex regional pain syndrome (CRPS) causes disabling and severe limb pain that is difficult to treat. The pain typically increases during motor actions, but is present also at rest. The pathophysiology of CRPS is incompletely understood. Some of the symptoms suggest involvement of the central nervous system, and accordingly, patients have been shown to display alterations in, for instance, the primary sensorimotor cortex (SM1) and indications of neuroinflammation. More thorough pathophysiological knowledge of CRPS would help to develop better treatments and diagnostics. My thesis includes four studies exploring the cerebral basis of CRPS. All patients participating in these studies suffered from unilateral upper-limb CRPS. Studies I and II explored the complex couplings between pain, motor actions and visual information in CRPS. In healthy persons, observation and imagery of motor actions are known to elicit brain activation in similar brain areas as does action execution. CRPS patients experience pain while they execute or imagine actions and at the same time their brain activity is abnormal. However, these phenomena have not previously been studied for action observation in CRPS. In Study I, ratings of subjective experiences (e.g. pain) during observation of others’ actions were compared between 19 CRPS patients and 19 healthy control subjects. We found that CRPS patients experienced observation of motor actions as unpleasant and painful, and they overestimated the force applied in the observed actions. In Study II, the brain responses to action observation, measured with functional magnetic resonance imaging (fMRI), were compared between 13 CRPS patients and 13 healthy control subjects using multivariate pattern analysis (MVPA). During painful action-observation, the patients displayed abnormal activity in, for example, the representation area of the painful limb in the SM1 as well as in other brain areas important for pain experience and motor actions. With MVPA, these abnormal activations reliably discriminated CRPS patients from healthy subjects, indicating potential of fMRI responses as biomarkers for CRPS. Together Studies I and II build the grounds for future studies on using action observation as an add-on treatment for CRPS. Study III elucidated alterations of brain functioning during spontaneous pain in CRPS. Comparison of resting-state fMRI between 12 CRPS patients and 17 healthy control subjects showed disrupted functional connectivity of the SM1 in CRPS, especially for the representation areas of the painful and contralateral non-painful limb. These results suggest that pain alters SM1 functions even during rest, disrupting normal brain processes that could e.g. support motor learning. In Study IV, volumes of brain structures, measured with magnetic resonance imaging, were compared between 12 CRPS patients, 8 non-CRPS pain patients and 12 healthy control subjects. In the CRPS patients, the right-ventricle choroid plexus was about one-fifth larger than in healthy subjects and about one-eight larger than in non-CRPS patients. Choroid plexus is important in e.g. neuroinflammation and this finding may open new lines in research for the pathogenesis and treatment of CRPS. In conclusion, these studies revealed novel brain-derived symptoms and signs of CRPS. Brain changes involved especially areas that have already previously been studied in CRPS (e.g. the representation areas of the painful and contralateral non-painful limb in the SM1) but also other areas, such as choroid plexus. The findings further corroborate central nervous system involvement in CRPS.
Original languageEnglish
Place of PublicationHelsinki
Print ISBNs978-951-51-3088-4
Electronic ISBNs978-951-51-3089-1
Publication statusPublished - 2017
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3112 Neurosciences
  • 3124 Neurology and psychiatry

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