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BACKGROUND: Phantom limb pain is a debilitating condition for which no effective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation. METHODS: Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specific frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials.gov, number NCT02281539. FINDINGS: Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically significant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1·0 [0·8]; p=0·001) for weighted pain distribution, 32% (38; absolute mean change 1·6 [1·8]; p=0·007) for the numeric rating scale, and 51% (33; absolute mean change 9·6 [8·1]; p=0·0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2·4 [2·3]; p=0·004) and 61% (39; absolute mean change 2·3 [1·8]; p=0·001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment. INTERPRETATION: Our findings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identified side-effects at present. FUNDING: Promobilia Foundation, VINNOVA, Jimmy Dahlstens Fond, PicoSolve, and Innovationskontor Väst.

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One of the current challenges in the field of advanced prosthetics is the development of artificial limbs that provide the user with detailed sensory feedback. Sensory feedback from our limbs is not only important for proprioceptive awareness and motor control, but also essential for providing us with a feeling of ownership or simply put, the sensation that our limbs actually belong to ourselves. The strong link between sensory feedback and ownership has been repeatedly demonstrated with the so-called rubber hand illusion (RHI), during which individuals are induced with the illusory sensation that an artificial hand is their own. In healthy participants, this occurs via integration of visual and tactile signals, which is primarily supported by multisensory regions in premotor and intraparietal cortices. Here, we describe a functional magnetic resonance imaging (fMRI) study with two upper limb amputees, showing for the first time that the same brain regions underlie ownership sensations of an artificial hand in this population. Albeit preliminary, these findings are interesting from both a theoretical as well as a clinical point of view. From a theoretical perspective, they imply that even years after the amputation, a few seconds of synchronous visuotactile stimulation are sufficient to activate hand-centered multisensory integration mechanisms. From a clinical perspective, they show that a very basic sensation of touch from an artificial hand can be obtained by simple but precisely targeted stimulation of the stump, and suggest that a similar mechanism implemented in prosthetic hands would greatly facilitate ownership sensations and in turn, acceptance of the prosthesis.

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OBJECTIVES: There is evidence that amputation leads to cortical reorganization, and it has been suggested that phantom pain might be related to a consequently emerging incongruence of motor intention, somatosensation and visual feedback. One therapeutic approach that has the potential to temporarily resolve this visuo-proprioceptive dissociation is mirror therapy, during which amputees typically move their intact limb while observing its reflection in a mirror, which in turn evokes the illusory perception of movement of their phantom limb. However, while the action of moving the phantom relieves pain for some patients, it can actually increase cramping sensations in others. In the current study we therefore implemented an alternative version of the mirror therapy involving a visuotactile illusion, to explore whether it might be effective with amputees for whom the action of moving the phantom increases phantom pain. METHODS: We recruited six upper limb amputees who had been previously exposed to the classical mirror therapy with no or limited success, and exposed them to two differential experimental conditions involving visualization paired with either illusory movement or illusory touch of the phantom hand. RESULTS: While none of the participants benefitted from the movement condition, five participants showed a significant pain reduction during the stroking condition. DISCUSSION: Albeit preliminary, our results represent an encouraging finding of possible future clinical relevance, and indicate that the type of multisensory stimulation that most efficiently reduces phantom pain can vary in different sub-populations of amputees.

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Most amputees experience phantom limbs, or the sensation that their amputated limb is still attached to the body. Phantom limbs can be perceived in the location previously occupied by the intact limb, or they can gradually retract inside the stump, a phenomenon referred to as "telescoping". Telescoping is relevant from a clinical point of view, as it tends to be related to increased levels of phantom pain. In the current study we demonstrate how a full-body illusion can be used to temporarily revoke telescoping sensations in upper limb amputees. During this illusion participants view the body of a mannequin from a first person perspective while being subjected to synchronized visuo-tactile stimulation through stroking, which makes them experience the mannequin's body as their own. In Experiment 1 we used an intact mannequin, and showed that amputees can experience ownership of an intact body as well as referral of touch from both hands of the mannequin. In Experiment 2 and 3 we used an amputated mannequin, and demonstrated that depending on the spatial location of the strokes applied to the mannequin, participants experienced their phantom hand to either remain telescoped, or to actually be located below the stump. The effects were supported by subjective data from questionnaires, as well as verbal reports of the perceived location of the phantom hand in a visual judgment task. These findings are of particular interest, as they show that the temporary revoking of telescoping sensations does not necessarily have to involve the visualization of an intact hand or illusory movement of the phantom (as in the rubber hand illusion or mirror visual feedback therapy), but that it can also be obtained through mere referral of touch from the stump to the spatial location corresponding to that previously occupied by the intact hand. Moreover, our study also provides preliminary evidence for the fact that these manipulations can have an effect on phantom pain sensations.

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We describe how upper limb amputees can be made to experience a rubber hand as part of their own body. This was accomplished by applying synchronous touches to the stump, which was out of view, and to the index finger of a rubber hand, placed in full view (26 cm medial to the stump). This elicited an illusion of sensing touch on the artificial hand, rather than on the stump and a feeling of ownership of the rubber hand developed. This effect was supported by quantitative subjective reports in the form of questionnaires, behavioural data in the form of misreaching in a pointing task when asked to localize the position of the touch, and physiological evidence obtained by skin conductance responses when threatening the hand prosthesis. Our findings outline a simple method for transferring tactile sensations from the stump to a prosthetic limb by tricking the brain, thereby making an important contribution to the field of neuroprosthetics where a major goal is to develop artificial limbs that feel like a real parts of the body.

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