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      Phantom limb pain: a case of maladaptive CNS plasticity?

      , ,
      Nature Reviews Neuroscience
      Springer Science and Business Media LLC

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          Abstract

          Phantom pain refers to pain in a body part that has been amputated or deafferented. It has often been viewed as a type of mental disorder or has been assumed to stem from pathological alterations in the region of the amputation stump. In the past decade, evidence has accumulated that phantom pain might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human studies and derive suggestions for innovative interventions aimed at alleviating phantom pain.

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          Most cited references91

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          Touching a rubber hand: feeling of body ownership is associated with activity in multisensory brain areas.

          In the "rubber-hand illusion," the sight of brushing of a rubber hand at the same time as brushing of the person's own hidden hand is sufficient to produce a feeling of ownership of the fake hand. We shown previously that this illusion is associated with activity in the multisensory areas, most notably the ventral premotor cortex (Ehrsson et al., 2004). However, it remains to be demonstrated that this illusion does not simply reflect the dominant role of vision and that the premotor activity does not reflect a visual representation of an object near the hand. To address these issues, we introduce a somatic rubber-hand illusion. The experimenter moved the blindfolded participant's left index finger so that it touched the fake hand, and simultaneously, he touched the participant's real right hand, synchronizing the touches as perfectly as possible. After approximately 9.7 s, this stimulation elicited an illusion that one was touching one's own hand. We scanned brain activity during this illusion and two control conditions, using functional magnetic resonance imaging. Activity in the ventral premotor cortices, intraparietal cortices, and the cerebellum was associated with the illusion of touching one's own hand. Furthermore, the rated strength of the illusion correlated with the degree of premotor and cerebellar activity. This finding suggests that the activity in these areas reflects the detection of congruent multisensory signals from one's own body, rather than of visual representations. We propose that this could be the mechanism for the feeling of body ownership.
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            Synaesthesia in phantom limbs induced with mirrors.

            Although there is a vast clinical literature on phantom limbs, there have been no experimental studies on the effects of visual input on phantom sensations. We introduce an inexpensive new device--a 'virtual reality box'--to resurrect the phantom visually to study inter-sensory effects. A mirror is placed vertically on the table so that the mirror reflection of the patient's intact had is 'superimposed' on the felt position of the phantom. We used this procedure on ten patients and found the following results. 1. In six patients, when the normal hand was moved, so that the phantom was perceived to move in the mirror, it was also felt to move; i.e. kinesthetic sensations emerged in the phantom. In D.S. this effect occurred even though he had never experienced any movements in the phantom for ten years before we tested him. He found the return of sensations very enjoyable. 2. Repeated practice led to a permanent 'disappearance' of the phantom arm in patient D.S. and the hand became telescoped into the stump near the shoulder. 3. Using an optical trick, impossible postures--e.g. extreme hyperextension of the fingers--could be induced visually in the phantom. In one case this was felt as a transient 'painful tug' in the phantom. 4. Five patients experienced involuntary painful 'clenching spasms' in the phantom hand and in four of them the spasms were relieved when the mirror was used to facilitate 'opening' of the phantom hand; opening was not possible without the mirror. 5. In three patients, touching the normal hand evoked precisely localized touch sensations in the phantom. Interestingly, the referral was especially pronounced when the patients actually 'saw' their phantom being touched in the mirror. Indeed, in a fourth patient (R.L.) the referral occurred only if he saw his phantom being touched: a curious form of synaesthesia. These experiments lend themselves readily to imaging studies using PET and fMRI. Taken collectively, they suggest that there is a considerable amount of latent plasticity even in the adult human brain. For example, precisely organized new pathways, bridging the two cerebral hemispheres, can emerge in less than three weeks. Furthermore, there must be a great deal of back and forth interaction between vision and touch, so that the strictly modular, hierarchical model of the brain that is currently in vogue needs to be replaced with a more dynamic, interactive model, in which 're-entrant' signalling plays the main role.
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              A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.

              Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.
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                Author and article information

                Journal
                Nature Reviews Neuroscience
                Nat Rev Neurosci
                Springer Science and Business Media LLC
                1471-003X
                1471-0048
                November 2006
                November 2006
                : 7
                : 11
                : 873-881
                Article
                10.1038/nrn1991
                17053811
                081a9a93-8bcd-4fb4-8177-4d0cb8d7a774
                © 2006

                http://www.springer.com/tdm


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