[Pathogenetic mechanisms of phantom-pain syndrome].

This review considers the literature data on the epidemiology of phantom-pain syndrome (PPS) presents the results of numerous clinical studies demonstrating the lack of effectiveness of the vast majority of modem non-pharmacological and pharmacological methods of treatment of PPS. Detail presents data on the patho genetic mechanisms underlying the PPS. According to most researchers, the major role in the patho genesis of the PPS has the reorganization of the somatosensory area of the cerebral cortex of the brain. At the same time discusses the views of researchers who believe that the main reason PPS is to strengthen nociceptive and nonnociceptive afferentation in the peripheral newous system. The comparison of these conflicting data it is concluded that in the genesis of the PPS plays the role of both primary and secondary sensitization. Leading important dysfunction of the central nervous system. Details the modern understanding of the mechanisms underlying the high efficiency of suppression of PPS during stimulation of motor cortex.

Gray matter changes following limb amputation with high and low intensities of phantom limb pain.

Limb amputation and chronic phantom limb pain (PLP) are both associated with neural alterations at all levels of the neuraxis. We investigated gray matter volume of 21 upper limb amputees and 14 healthy control subjects. Results demonstrate that amputation is associated with reduced gray matter in areas in the motor cortex representing the amputated limb. Additionally, patients show an increase in gray matter in brain regions that belong to the dorsal and ventral visual stream. We subdivided the patient group into patients with medium to high PLP (HPLP; N = 11) and those with slight PLP (SPLP; N = 10). HPLP patients showed reduced gray matter in brain areas involved in pain processing. SPLP patients showed a significant gray matter increase in regions of the visual stream. Results indicate that all patients may have an enhanced need for visual control to compensate the lack of sensory feedback of the missing limb. As we found these alterations primarily in the SPLP patient group, successful compensation may have an impact on PLP development. Therefore, we hypothesize that visual adaptation mechanisms may compensate for the lack of sensorimotor feedback and may therefore function as a protection mechanism against high PLP development.

Phantom eye syndrome: a review of the literature.

The purpose of this literature review was to describe the main features of phantom eye syndrome in relation to their possible causes, symptoms, treatments, and influence of eye amputation on quality of life of anophthalmic patients. For this, a bibliographical research was performed in Pubmed database using the following terms: "eye amputation," "eye trauma," "phantom eye syndrome," "phantom pain," and "quality of life," associated or not. Thirteen studies were selected, besides some relevant references contained in the selected manuscripts and other studies hallowed in the literature. Thus, 56 articles were included in this review. The phantom eye syndrome is defined as any sensation reported by the patient with anophthalmia, originated anophthalmic cavity. In phantom eye syndrome, at least one of these three symptoms has to be present: phantom vision, phantom pain, and phantom sensations. This syndrome has a direct influence on the quality of life of the patients, and psychological support is recommended before and after the amputation of the eyeball as well as aid in the treatment of the syndrome. Therefore, it is suggested that, for more effective treatment of phantom eye syndrome, drug therapy should be associated with psychological approach.

Enhanced corticospinal response to observed pain in pain synesthetes.

Observing noxious injury to another's hand is known to induce corticospinal inhibition that can be measured in the observer's corresponding muscle. Here, we investigated whether acquired pain synesthetes, individuals who experience actual pain when observing injury to another, demonstrate less corticospinal inhibition than do controls during pain observation, as a potential mechanism for the experience of vicarious pain. We recorded motor-evoked potentials (MEPs) induced at two time points through transcranial magnetic stimulation while participants observed videos of a hand at rest, a hypodermic needle penetrating the skin, a Q-tip touching the skin, and a hypodermic needle penetrating an apple. We compared MEPs in three groups: 7 amputees who experience pain synesthesia, 11 nonsynesthete amputees who experience phantom limb pain, and 10 healthy controls. Results indicated that the pain synesthete group demonstrated significantly enhanced MEP response to the needle penetrating the hand, relative to the needle not having yet penetrated the hand, as compared with controls. This effect was not observed exclusively in the same muscle where noxious stimulation was applied. We speculate that our findings reflect a generalized response to pain observation arising from hyperactivity of motor mirror neurons not involved in direct one-to-one simulation but, rather, in the representation of another's experience.

Interdependence of movement and anatomy persists when amputees learn a physiologically impossible movement of their phantom limb.

The feeling we have of our own body, sometimes called "body image," is fundamental to self-awareness. However, by altering sensory input, the body image can be modified into impossible configurations. Can impossible movements of the body image be conjured solely via internally generated mechanisms, and, if so, do the structural characteristics of the body image modify to accommodate the new movements? We encouraged seven amputees with a vivid phantom arm to learn to perform a phantom wrist movement that defied normal anatomical constraints. Four reported success. Learning the impossible movement coincided in time with a profound change in the body image of the arm, including a sense of ownership and agency over a modified wrist joint. Remarkably, some previous movements and functional tasks involving the phantom arm became more difficult once the shift in body image had occurred. Crucially, these introspective reports were corroborated by robust empirical data from motor imagery tasks, about which amputees were naïve and to which assessors were blind. These results provide evidence that: a completely novel body image can be constructed solely by internally generated mechanisms; that the interdependence between movement repertoire and structural constraints of the body persists even when the structural constraints imparted by the body do not--the body image we construct still constrains imagined movements; and that motor learning does not necessarily need sensory feedback from the body or external feedback about task performance.

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields.

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0-10 verbal numerical rating scale. Most of the patients (n = 10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n = 5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.

Central mechanisms of experimental and chronic neuropathic pain: findings from functional imaging studies.

Over the last few years remarkable efforts have been made using functional imaging studies to unravel brain processing of pain and decipher underlying neuronal mechanisms. Cerebral processing in experimental pain models, especially those provoking hyperalgesia, and its pharmacological modulation will form the first part of this review. In a second part we will address central mechanisms of clinical neuropathic pain. Up to now, there are at least six main mechanisms involved in the chronification of neuropathic pain: (i) activity increase in areas of the pain neuromatrix, (ii) recruitment of additional cortical areas beyond the classical pain neuromatrix, (iii) cortical reorganization and maladaptive neuroplasticity, (iv) alterations in neurochemistry (v) structural brain changes and (vi) disruption of the brain default mode network. In a third part of this review we discuss mechanisms of endogenous pain modulation.

Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.

Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery.

Using functional MRI (fMRI) we investigated 13 upper limb amputees with phantom limb pain (PLP) during hand and lip movement, before and after intensive 6-week training in mental imagery. Prior to training, activation elicited during lip purse showed evidence of cortical reorganization of motor (M1) and somatosensory (S1) cortices, expanding from lip area to hand area, which correlated with pain scores. In addition, during imagined movement of the phantom hand, and executed movement of the intact hand, group maps demonstrated activation not only in bilateral M1 and S1 hand area, but also lip area, showing a two-way process of reorganization. In healthy participants, activation during lip purse and imagined and executed movement of the non-dominant hand was confined to the respective cortical representation areas only. Following training, patients reported a significant reduction in intensity and unpleasantness of constant pain and exacerbations, with a corresponding elimination of cortical reorganization. Post hoc analyses showed that intensity of constant pain, but not exacerbations, correlated with reduction in cortical reorganization. The results of this study add to our current understanding of the pathophysiology of PLP, underlining the reversibility of neuroplastic changes in this patient population while offering a novel, simple method of pain relief.

Dorsal root entry zone lesions for phantom limb pain with brachial plexus avulsion: a study of pain and phantom limb sensation.

BACKGROUND: Lesions in the dorsal root entry zone (DREZ) have been shown to be significantly effective in relieving the pain of brachial plexus avulsion (BPA), but they have a limited effect on phantom limb pain (PLP). There is still the question remaining of whether DREZ lesions are effective in treating PLP in cases of BPA. METHODS: Our study includes 14 post-traumatic patients with BPA and upper limb amputation. All developed PLP and underwent DREZ lesions. After the surgery, patients were asked to estimate the global percent of pain relief (0-100%). The phantom limb sensation (PLS) was also inquired after. RESULTS: Overall, 9 (64.3%) of 14 patients had satisfactory pain relief; the mean follow-up was 15.2 +/- 6.6 months. Among the 9 patients with satisfactory pain relief, PLS had altered in 6 (66.7%), while, in the other 5 patients with poor pain relief, none had experienced alterations in PLS. CONCLUSION: DREZ lesions are effective in the treatment of PLP with BPA. Alteration in PLS after the surgery may be a predictive factor for good pain relief. The good response of PLP patients with BPA to DREZ lesions suggests that an evaluation of the cervical dorsal roots should be conducted in patients with post-traumatic PLP.

A review of current theories and treatments for phantom limb pain.

Following amputation, most amputees still report feeling the missing limb and often describe these feelings as excruciatingly painful. Phantom limb sensations (PLS) are useful while controlling a prosthesis; however, phantom limb pain (PLP) is a debilitating condition that drastically hinders quality of life. Although such experiences have been reported since the early 16th century, the etiology remains unknown. Debate continues regarding the roles of the central and peripheral nervous systems. Currently, the most posited mechanistic theories rely on neuronal network reorganization; however, greater consideration should be given to the role of the dorsal root ganglion within the peripheral nervous system. This Review provides an overview of the proposed mechanistic theories as well as an overview of various treatments for PLP.

[Comparison of phantom limb pain or phantom extremity sensation of upper and lower extremity amputations]. / Alt ve üst ekstremite amputasyonlarinin fantom agrisi ve fantom ekstremite hissi yönünden karsilastirilmasi.

The aim of this retrospective study is to evaluate the upper and the lower extremity amputations with regard to phantom pain, phantom sensation and stump pain. A questionnaire consisting of 23 questions was send to the patients who underwent upper or lower extremity amputation surgery between 1996- 2005. The patients were questioned for the presence of phantom pain and sensations and if they existed for the frequency, intensity, cause of amputation, pre-amputation pain, stump pain, usage of artificial limb. Totally 147 patients were included and the response rate was 70 %. The incidence of phantom pain in Upper Extremity Group was 60 % and 65.8% in Lower Extremity Group. The incidence of phantom sensations was 70.7% in Upper Extremity Group and 75.6% in Lower Extremity Group. There was no significant difference between two groups considering in phantom pain and phantom sensations. The phantom pain was significantly higher in patients who lost dominant hand, experienced pre amputation pain and suffered stump pain. There were no significant differences in regard to phantom pain and sensation between upper and lower extremity amputations. However the presence of preamputation pain, stump pain and amputation of dominant hand were found as risk factors for the development of phantom pain.

Ultrasound Findings of Young and Traumatic Amputees With Lower Extremity Residual Limb Pain in Turkey.

OBJECTIVE: The current study was designed to document clinical and ultrasound (US) findings of patients with residual limb pain (RLP) after amputation and to investigate the relationship between these findings. MATERIALS AND METHODS: A chart review was performed to identify demographic and clinical data including the age (current and at the time of injury), time since amputation, gender, reason for amputation, affected limb number, side and level of limb loss, and ultrasonographic findings of young and traumatic amputees with RLP. RESULTS: The study included a total of 147 patients. Inflammation and neuroma were the leading pathologies in 20-29 years and 30-39 years age groups, respectively. Inflammation/edema were detected significantly more in patients with <1 year since amputation (P = 0.001). Neuroma was found at a significantly high rate in patients at 1-5 years (P = 0.029) and infection/abscess was more common in patients at >5 years since amputation (P = 0.051). The percentage of neuromas in below-the-knee amputees was significantly higher than in non-below-the-knee amputees (45.8% vs. 28.6%). Neuroma formation was detected in 50% of the patients with land mine-related amputation and at 27% in patients with amputation secondary to other traumatic reasons. Regression analysis showed below-the-knee-level amputation to be an associated factor for US abnormality. CONCLUSION: The leading US findings were inflammation/edema, neuroma, and infection/abscess in traumatic amputees with RLP. The US findings might be different in patients according to the time since amputation. Patient with land mine-related amputations may have different US findings.

Treatment of neuropathic pain in Sierra Leone.

During Sierra Leone's violent decade-long war, the warring parties used amputation, especially of arms, as a means of terror. In a camp for amputees in the capital city Freetown, Médecins Sans Frontières established a clinic and a treatment programme for neuropathic pain. Insecurity and cultural and language barriers have complicated this work, but medical and humanitarian benefits have been demonstrated. Pain services are virtually non-existent in less-developed countries. There have recently been no major treatment advances for neuropathic or phantom pain; however, the general body of knowledge about amputation pain can be increased by observations from these difficult settings.

Neuronal activity in the region of the thalamic principal sensory nucleus (ventralis caudalis) in patients with pain following amputations.

Thalamic neuronal activity has not been studied in a primate model of peripheral nerve injury. We now report neuronal activity in the region of the human principal sensory nucleus of thalamus (ventralis caudalis) in awake patients during the physiologic exploration that precedes surgical procedures for treatment of stump pain and movement disorders. All patients with amputations showed increased thalamic representations of the stump as reflected in both receptive and projected field maps. This suggested that thalamic re-organization involved both the afferent inputs from and the perceptual representation of the limb. The spontaneous activity of neurons in the region of ventralis caudalis representing the limb with the stump (stump area) was significantly different from that in other areas of the region of ventralis caudalis in patients with amputations (stump control areas) and in patients with movement disorders (control areas). The mean interspike intervals were significantly shorter for cells located in stump areas than for those located in stump control or control areas. Cells in all areas were found to fire in three different patterns: B group (burst) characterized by bursting activity, R group (relay) characterized as a Poisson process, and III group characterized by non-bursting, non-Poisson activity. Cells in the B group were significantly more common in stump control (41%) and stump areas (33%) than in control areas (15%). Bursting cells were found to have patterns consistent with the occurrence of a calcium spike (spike-burst pattern). The spike-burst pattern was most common among cells with receptive fields in the stump area. In these cells firing between bursts (primary event rate) was significantly higher than other cells in the region of ventralis caudalis, suggesting that spike-bursts are not due to hyperpolarization, i.e. low-threshold spikes. Spike-bursts often occur as a result of low-threshold spikes, when the cell is hyperpolarized. In contrast, spike-bursts in these patients were associated with increased interburst firing rates in cells with receptive fields. Thus bursting of these cells may have been due to high-threshold dendritic calcium spikes evoked by afferent input. In that case bursting could be involved in activity-dependent changes in thalamic function following deafferentation through a calcium-mediated mechanism.

Central noradrenergic blockade prevents autotomy in rat: implication for pharmacological prevention of postdenervation pain syndrome.

Following transection of peripheral nerve, rats exhibit autotomy, which is considered to be the animal model of postdenervation pain syndrome. It has been suggested that phantom limb pain is a result of peripheral denervation leading to reorganization of somatosensory pathways, particularly in the cerebral cortex, which is shown to depend upon central noradrenergic activity. In this study, sciatic and saphenous nerves were sectioned in the left hindpaw of 30 adult rats resulting in complete loss of pain sensation in the hindpaw. A group of rats received normal saline, compared to another group which received N-(2-) Chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) injection 24 h prior to transection. The latter group was also compared to a third group whose central noradrenergic system were also blocked by bilateral injection of 6-OHDA into the ascending noradrenergic bundle 1 week prior to transection. A fourth group received contralateral cortical ablation in addition to peripheral nerve transection and was compared to the first group whose cortex remained intact. The animals were observed daily for 60 days and autotomy was scored in accordance to the system of Wall et al. After 1 week, control animals began to exhibit autotomy. In contrast, autotomy was absent in rats treated with DSP4, similar to rats which received 6-OHDA. Rats which had contralateral cortical ablation showed a considerably delayed onset of autotomy and a reduction in final autotomy scores. We conclude that autotomy, as a model of postdenervation pain syndrome, can be prevented by blockade of noradrenergically mediated cortical reorganization. The clinical implications of this finding are discussed.

Motor and parietal cortex stimulation for phantom limb pain and sensations.

Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2 mA, 15 min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.

Health services utilization in adult acquired major upper-limb amputees: a population-based survey.

OBJECTIVE: To increase knowledge of health services utilization and related factors in adult acquired major upper-limb amputees. DESIGN: Population-based cross-sectional study conducted in Norway. SUBJECTS: Two hundred and twenty four adult acquired major upper-limb amputees (57.4% response rate). Mean age was 53.7 years, 83.5% were men and mean post-amputation time was 24.0 years. METHODS: Data were collected by postal questionnaires. Amputation-related health services utilization, perceived benefit and unmet needs were reported and associations between these factors and background factors were estimated by multivariate logistic regression analyses. RESULTS: Reported health services utilization was relatively low. The reported benefit of utilized services was generally high. For several non-utilized services, considerable unmet needs for utilization were reported. Several background factors were significantly associated with different aspects of the services examined. A considerable discrepancy between reported pain and utilization of specified pain treatments was noted. CONCLUSION: The findings of this study suggest that several health services available to acquired major upper-limb amputees should be strengthened. Establishing routines to ensure access to optimal, individualized rehabilitation may prevent disability. We recommend additional, longitudinal studies to further assess the need for mental health care and pain treatment in acquired major upper-limb amputees.

The contribution of sympathetic mechanisms to postamputation phantom and residual limb pain: a pilot study.

UNLABELLED: Postamputation pain (PAP) affects over 60% of major limb amputees. One of the main challenges in treating PAP is the difficulty involved in identifying pain mechanism(s), which pertains to both residual limb pain (RLP) and phantom limb pain (PLP). In this study, sympathetic blocks were performed on 17 major limb amputees refractory to treatment, including 2 placebo-controlled blocks done for bilateral amputations. One hour postinjection, mean RLP scores at rest declined from 5.2 (SD 2.8) to 2.8 (SD 2.6) (P = .0002), and PLP decreased from 5.3 (SD 3.1) to 2.3 (SD 2.1) (P = .0009). By 1 week, mean pain scores for RLP and PLP were 4.3 (SD 2.9) and 4.2 (SD 3.0), respectively. Overall, 8 of 16 (50%) patients experienced ≥50% reduction in RLP 1-hour postinjection, with the beneficial effects being maintained at 1 and 8 weeks in 4 and 1 patient(s), respectively. For PLP, 8 of 15 (53%) patients obtained ≥50% decrease in pain 1-hour postblock, with these numbers decreasing to 2 patients at both 1 and 8 weeks. In the 2 bilateral amputees who received controlled injections, mean PLP and RLP at rest scores went from 4.0 and 3.3 to 4.0 and 2.5 1-hour postblock, respectively, on the placebo side. On the treatment side, mean PLP and RLP scores decreased from 7.5 and 6.5, respectively, to 0. PERSPECTIVE: The results of this study suggest that sympathetic mechanisms play a role in PLP and to a lesser extent, RLP, but that blocks confer long-term benefits in only a small percentage of patients.

The missing hands of Blaise Cendrars.

The life and works of Blaise Cendrars (1887-1961), one of the greatest French literary authors of the 20th century, were profoundly influenced by neurology. Having been wounded in the Great War in 1915, his right forearm was amputated, and he very quickly began to suffer from stump pain and phantom hand phenomena, which persisted until his death. Following his amputation he became a left-handed writer. Half a century later, between 1956 and his death in 1961, he suffered two strokes which gradually paralyzed the left side of his body. After the second stroke in 1958, he became a 'handless writer', also partially losing his ability to express himself orally. Although the works of Blaise Cendrars portray characters with serious mental disorders, they also contain characters with real neurological diseases, such as the trepanated aphasic in 'J'ai Saigné'. The most famous of these is undoubtedly Moravagine, the protagonist of the eponymous novel, who presents acute behavioral disturbances. We learn from the autopsy report that he was in fact suffering from a brain tumor. On several occasions, including the complex case of Moravagine, and by presenting his ideas on hysteria, Blaise Cendrars, in his own way, addressed the somewhat fuzzy boundary that exists between psychiatry and neurology.