Phantom pain is associated with preserved structure and function in the former hand area
TL;DR: It is proposed that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top–down inputs.
Abstract: Phantom pain after arm amputation is widely believed to arise from maladaptive cortical reorganization, triggered by loss of sensory input. We instead propose that chronic phantom pain experience drives plasticity by maintaining local cortical representations and disrupting inter-regional connectivity. Here we show that, while loss of sensory input is generally characterized by structural and functional degeneration in the deprived sensorimotor cortex, the experience of persistent pain is associated with preserved structure and functional organization in the former hand area. Furthermore, consistent with the isolated nature of phantom experience, phantom pain is associated with reduced inter-regional functional connectivity in the primary sensorimotor cortex. We therefore propose that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top-down inputs. Our results prompt a revisiting of the link between phantom pain and brain organization.
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TL;DR: In this paper, the effects of daily mirror training over 4 weeks in 13 chronic phantom limb pain patients after unilateral arm amputation were investigated, and fMRI data analyses revealed a relationship between change in pain after mirror therapy and a reversal of dysfunctional cortical reorganization in primary somatosensory cortex.
243 citations
Cites background or methods from "Phantom pain is associated with pre..."
...In order to assess the contribution of the hand movement (cf. Makin et al., 2013), we also defined functional hand ROIs using group means of M1 and S1 during hand movement (contralateral to amputation site) and defined 5-mm spherical ROIs around these coordinates....
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...Makin et al. (2013) used the intensity of activation, whereas cortical reorganization mainly relates to its location....
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...Makin et al. (2013) recently hypothesized that preserved hand function rather than dysfunctional reorganization (Flor et al., 1995) in S1 is positively associated with PLP, suggesting that an effective PLP treatment should be accompanied by reduced activity in the hand representation in S1 rather…...
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TL;DR: This article critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions.
Abstract: Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.
223 citations
TL;DR: Intraforaminal injection of lidocaine eliminated phantom limb pain in amputees, suggesting that its primary driver is hyperexcitable afferent neurons rather than maladaptive cortical plasticity, and recommends the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain.
Abstract: Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). What is the origin of these sensations? There is currently a broad consensus among investigators that PLP is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRGs) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation (npPLS). Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. The suppression of PLP and npPLS could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within the DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain.
212 citations
Cites background from "Phantom pain is associated with pre..."
...In fact, the cortical representation of the (phantom) limb actually increases, as one might predict given the ectopia coming off stump neuromas and the DRG [45]....
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TL;DR: 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.
167 citations
TL;DR: A new prosthetic leg that can transmit sensory signals via implanted electrodes is shown to restore meaningful sensory feedback that improves walking performance and lowers phantom limb pain during use in two human lower-limb amputees.
Abstract: Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1–4. The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg5,6. To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes7 in the remaining tibial nerve (ClinicalTrials.gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback. A new prosthetic leg that can transmit sensory signals via implanted electrodes is shown to restore meaningful sensory feedback that improves walking performance and lowers phantom limb pain during use in two human lower-limb amputees.
152 citations
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TL;DR: An automated method for segmenting magnetic resonance head images into brain and non‐brain has been developed and described and examples of results and the results of extensive quantitative testing against “gold‐standard” hand segmentations, and two other popular automated methods.
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TL;DR: A very strong direct relationship is reported between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation, indicating that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
Abstract: Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
1,692 citations