Action Observation May Hold Promise as a Potential Therapy for Patients With CRPS

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The study showed that 7 brain regions were distinctly activated in CRPS vs control participants, in response to visualization of hand motion.
The study showed that 7 brain regions were distinctly activated in CRPS vs control participants, in response to visualization of hand motion.

Patients with Complex Regional Pain Syndrome (CRPS) may have impaired neural activity while observing others' motor activity, according to a study published in November in the Journal of Pain.1

In this study, women with upper limb CRPS (n=13; ages 31-58) and age-matched controls (n=13) were asked to visualize videos of hand motion, from the perspective of the hand owner, while in a functional magnetic resonance imaging (fMRI) scanner (3 Tesla).

The pathophysiology of CRPS -- characterized, among other symptoms, by pain, allodynia, and hyperesthesia, usually restricted to one limb — is still unclear, and is thought to arise from a combination of peripheral and central dysregulations, with the involvement of inflammatory processes and maladaptive neuroplasticity.2 In the absence of defined biomarkers, diagnosis of CRPS is based on highly subjective criteria.3

Visual distortion of the affected limb (eg, through magnification) was shown to modulate the pain perceived by CRPS patients,4 indicating “that the manipulation of visual input might lead to novel clinical applications.”1

Because pain in patients with CRPS is enhanced by motor imagery5 and by observing motor actions,6 in addition to movements, the authors of the present study hypothesized that imaging brains of CRPS patients who were observing actions might provide further insights into disease mechanisms.

The study showed that 7 brain regions (including the left sensory motor hand area, Brodmann area 45, and the right secondary somatosensory cortex) were distinctly activated in CRPS vs control participants, in response to visualization of hand motion.

The authors found that the most notable abnormalities in brain responses observed in CRPS patients were detected during the visualization of object squeezing with maximal force, perceived as painful by this group.

Functional MRI scans showed that brain regions involved in pain perception, motor control, and the action observation network showed stronger activation in CRPS patients. In particular, the inferior frontal gyrus, known to “mediate effects of attention, expectations and reappraisal during pain perception”7 was strongly activated in CRPS subjects.

The inferior frontal gyrus is thought to be involved in both motor and cognitive inhibition.8 The authors therefore concluded that “a dysfunctional inhibition related to aversive associations to motor actions might also explain the activation differences. Such dysfunction could be an important pathophysiological mechanism explaining many CNS-related features of CRPS.”

Another notable result was observed in the left primary sensorimotor cortex in patients with CRPS, which was activated in a somatotopic fashion, dependent of the observed body part, and thought by the researchers to result from a “simulation of the somatosensory content of the observed action.”

According to the authors, this “indicates that the dysfunction in the sensorimotor cortex also affects the neural processing of observed actions.”

The authors note that action observation—already part of motor rehabilitation therapy in Parkinson's disease—may also be effective in CRPS patients in whom this study showed it can “address the disruption” in the primary sensorimotor cortex affected in those patients.

Limitations

The study was conducted on a small number of patients (n=13), all of whom were females. Despite the fact that CRPS predominantly affects women (with a 3 to 4 time higher prevalence that in men), the responses might be gender-specific.

 

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References

  1. Hotta J, Saari J, Koskinen M, Hlushchuk Y, Forss N, Hari R. Abnormal brain responses to action observation in complex regional pain syndrome. J Pain. 2016. DOI: 10.1016/j.jpain.2016.10.017.
  2. Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10(7):637-648.
  3. Harden RN. Objectification of the diagnostic criteria for CRPS. Pain Med. 2010;11(8):1212-1215.
  4. Moseley GL, Parsons TJ, Spence C. Visual distortion of a limb modulates the pain and swelling evoked by movement. Curr Biol. 2008;18(22):R1047-8.
  5. Moseley GL, Zalucki N, Birklein F, Marinus J, Van hilten JJ, Luomajoki H. Thinking about movement hurts: the effect of motor imagery on pain and swelling in people with chronic arm pain. Arthritis Rheum. 2008;59(5):623-631.
  6. Hotta J, Harno H, Nummenmaa L, Kalso E, Hari R, Forss N. Patients with complex regional pain syndrome overestimate applied force in observed hand actions. Eur J Pain. 2015;19(9):1372-1381.
  7. Wiech K, Ploner M, Tracey I. Neurocognitive aspects of pain perception. Trends Cogn Sci (Regul Ed). 2008;12(8):306-313.
  8. Levy BJ, Wagner AD. Cognitive control and right ventrolateral prefrontal cortex: reflexive reorienting, motor inhibition, and action updating. Ann N Y Acad Sci. 2011;1224:40-62.
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