MicroRNA-Related Polymorphism and Their Association with Fibromyalgia.

MicroRNAs are tissue-specific expressed short RNAs that serve post-transcriptional gene regulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions, and in the 3'UTR of protein-coding genes. To identify disease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48,329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. Results show that 29 markers had p-values < 1 × 10-3, and the strongest association was observed for rs758459 (p-value of 0.0001), located in the Neurogenin 1 gene which is targeted by hsa-miR-130a-3p. Furthermore, variant rs2295963 is predicted to affect binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fibromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.

Cue-reactivity to distal cues in individuals at risk for gaming disorder.

BACKGROUND: Gaming disorder (GD) is a disorder due to addictive behaviors (ICD-11). Cue-reactivity and craving are relevant mechanisms in the development and maintenance of addictive behaviors. When confronted with cues showing in-game content (proximal cues) individuals with higher symptom severity show increased cue-reactivity. Based on conditioning and addiction theories on incentive sensitization, cue-reactivity responses may generalize to more distal cues, e.g. when individuals at risk of developing a GD are confronted with a starting page of an online game. In cue-reactivity paradigms so far, only proximal gaming cues have been used. METHODS: We investigated the effect of distal gaming cues compared to gaming-unrelated control cues on cue-reactivity and craving in 88 individuals with non-problematic use of online games (nPGU) and 69 individuals at risk for GD (rGD). The distal cues showed the use of an electronic device (e.g., desktop PC or smartphone) whose screen showed starting pages of either games (target cues), shopping- or pornography sites (control cues) from a first-person perspective. FINDINGS: We found significantly higher urge and arousal ratings as well as longer viewing times for gaming-related compared to gaming-unrelated control cues in rGD compared to nPGU. Valence ratings did not differ between groups. INTERPRETATION: The results demonstrate that already distal gaming-specific cues lead to cue-reactivity and craving in rGD. This finding indicates that based on conditioning processes, cue-reactivity and craving develop during the course of GD and generalize to cues that are only moderately related to the specific gaming activity.

Adverse effects of the COVID-19 pandemic on fibromyalgia patients in Germany: a longitudinal investigation including pre-pandemic data of pain and health-related outcomes.

OBJECTIVES: The COVID-19 pandemic, along with the associated restrictions and changes, has had a far-reaching impact on the mental health and well-being of people around the world. The most serious impact can arguably be observed in vulnerable populations, such as chronic pain patients. Using a pre-test/post-test design with pre-pandemic comparative data, the present study sought to investigate how the pandemic impacted chronic pain and well-being in individuals with fibromyalgia (FM) (N = 109). METHODS: We assessed longitudinal changes of various clinical parameters, such as pain severity, disability, FM impact, depressive mood and several items assessing the individual experience of the pandemic as well as self-perceived changes of pain, anxiety, depression and physical activity levels. RESULTS: Results suggested a significant self-perceived worsening of pain, depressive mood, anxiety as well as reduced physical activity due to the pandemic. Interestingly, these self-perceived changes were not reflected in longitudinal increases of test values (T1-T2). Pain severity at T1 was the strongest predictor of pain severity at T2, while COVID-related outcomes showed no critical importance, with COVID-related fear being the only significant predictor of T2 pain. The general perceived negative impact of the pandemic was the only predictor of self-perceived worsening of pain. Finally, patients with less severe pre-pandemic pain symptoms displayed greater longitudinal worsening of pain. CONCLUSIONS: These findings emphasise the importance of addressing the specific needs of chronic pain suffers during a pandemic.

Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study.

BACKGROUND: Previous studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes. METHODS: We used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores). RESULTS: VBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus. CONCLUSIONS: Our results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula.

Neural correlates of control over pain in fibromyalgia patients.

The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings.

Prevalence of Phantom Phenomena in Congenital and Early-Life Amputees.

Phantom limb pain (PLP) is a common consequence of the amputation of a limb. Persons with congenital limb absence (congenital amputees) or an acquired limb amputation at an early age seem to rarely experience PLP. However, the number of available studies and their sample sizes are low. In the present cross-sectional study, we assessed the presence of several phantom phenomena in a sample of 99 adult unilateral congenital amputees (con) of whom 34 had a limb correction later in life (limbc) and 153 adult participants with a unilateral amputation before the age of 6 years (subgroups: amputation between birth and 2 years (0-2y; n = 48), 3-4 years (3-4y; n = 46), and 5 to 6 years (5-6y; n = 59)). We found a higher prevalence and intensity of PLP in the 5-6y group compared to the other groups. Residual limb pain (RLP) intensity was higher in the 3 to 4 y and 5 to 6 y groups compared to the con group. Non-painful phantom limb sensation (PLS) intensity and telescoping intensity were higher in the 5 to 6 y group compared to the con and 0 to 2 y groups. Our results indicate that PLP prevalence as well as intensity is low when the limb loss happened before the age of 5 years. PERSPECTIVE: The prevalence of phantom limb pain, residual limb pain, and non-painful phantom limb sensation in congenital amputees and participants with an amputation early in life is low. This might be due to the missing or reduced nociceptive input from the residual limb to the brain and higher development-associated adaptability of the somatosensory system.

[Clinical updates on phantom limb pain : German version]. / Klinisches Update zu Phantomschmerz : Deutsche Fassung.

INTRODUCTION: Most patients with amputation (up to 80 %) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. METHODS: This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. RESULTS: The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. DISCUSSION: Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

Influencing the body schema through the feeling of satiety.

The body schema is a much discussed aspect of body awareness. Although there is still no single definition, there is widespread consensus that the body schema is responsible for movement and interaction with the environment. It usually remains outside of active consciousness. There are only few investigations on influences on the body schema and none of them investigated feeling of satiety or hunger. Thirty-two healthy women were investigated twice, one time sat and the other time hungry. To measure the body schema, we used a door-like-aperture and compared the critical aperture-to-shoulder-ratio (cA/S). A cover story was used to ensure that the unconscious body schema has been measured. We found a significantly higher cA/S for satiety compared to hungry, which indicates that during satiety participants rotate their shoulders for relatively larger door compared to hunger, unconsciously estimating their body size to be larger. We showed that even a moderate rated feeling of hunger or satiety leads to an adjustment in body-scaled action and consequently also an adaptation of body schema. It suggests that, in addition to the visual-spatial and the proprioceptive representation, somatic information can also be relevant for the body schema.

Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face.

BACKGROUND: The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. METHODS: In this study, we applied QST in 37 unilateral upper-limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. RESULTS: We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. CONCLUSION: We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms. SIGNIFICANCE: Phantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.

The Prevalence and Characteristics of Phantom Limb Pain and Non-Painful Phantom Phenomena in a Nationwide Survey of 3,374 Unilateral Limb Amputees.

The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP. PERSPECTIVE: Clinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain.

Watching Your Neck: The Influence of Real-Time Visual Feedback on Cervical Joint Position Sense in Chronic Neck Pain.

Patients with neck pain demonstrate a variety of sensorimotor impairments, such as decreased cervical joint position sense (CJPS) acuity, which might also be associated with an impaired internal body representation. The present study evaluated the effect of real-time visual feedback of the individual's own neck on CJPS compared to observing a book. Twenty-three patients with neck pain participated in the experiment and received the interventions in randomized order on separate days in a within-subject pretest-posttest design. Before and immediately after each intervention, CJPS was measured by a therapist blinded to the intervention. The results demonstrate a significantly different development of CJPS (p = .04), with increased CJPS acuity after observing one's own neck and decreased acuity after observing a book. Real-time visual feedback of the neck improved CJPS acuity in patients with neck pain without active movements of the neck, indicating the importance of central nervous system processing for CJPS acuity.

Addiction Research Unit: Affective and cognitive mechanisms of specific Internet-use disorders.

In the eleventh International Classification of Diseases (ICD-11) of the World Health Organization, gambling disorder and gaming disorder are included in the category 'disorders due to addictive behaviours', which can be specified further as occurring either predominantly offline or predominantly online. Other specific problematic behaviours may be considered for the category 'other specified disorders due to addictive behaviours'. The Research Unit FOR 2974, funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), focuses on the most prominent online addictive behaviours: gaming, pornography use, buying-shopping and social-networks use. The main goal of the Research Unit is to contribute to a better understanding of the common and differential psychological as well as neurobiological mechanisms involved in these specific types of Internet-use disorders. We aim to investigate theoretically argued (bio)psychological processes with a focus on concepts coming from research of substance-use disorders, for example, cue reactivity and craving, executive functions and specific inhibitory control, coping, implicit cognitions, and decision making. One central characteristic of the Research Unit is that we will investigate all participants using a comprehensive core battery of experimental paradigms, neuropsychological tasks, questionnaires, biomarkers, ambulatory assessment, and a 6-month follow-up survey. Beyond the anticipated contributions to the scientific understanding of the mechanisms involved in the development and maintenance of respective online addictive behaviours, we also expect contributions to clinical practice by showing which affective and cognitive mechanisms may be addressed more intensively to optimize treatment.

Disorder specific rewarding stimuli in anorexia nervosa.

OBJECTIVE: To enhance our understanding of reward stimuli in anorexia nervosa (AN) and to provide a basis for future research on reward processes, disorder specific reward stimuli as well as primary and secondary reinforcers were investigated. METHOD: We developed a set of pictures with "disorder specific reward" stimuli, with the six subcategories "sport," "losing weight," "healthy food," "discipline," "thin bodies," "appreciation of others," and evaluated reward ratings of these "disorder specific reward" stimuli as well as "erotic," "high caloric," and "neutral" stimuli in 25 patients with AN and 25 participants in the comparison group (CG). RESULTS: We found a significant main effect for picture category and a significant interaction. The reward ratings were higher in patients with AN compared with CG for the "disorder specific reward" stimuli. In the reward subcategories, patients with AN had higher reward ratings compared with CG in all categories except of healthy food. The "disorder specific reward" stimuli of the categories "sport," "losing weight," and "healthy food" showed higher reward ratings compared with the categories "discipline," "thin bodies," and "appreciation of others" in patients with AN. DISCUSSION: The previously used category "thin bodies" used to investigate the reward system might be less effective compared with stimuli from the categories "sport," "losing weight," and "healthy food."

Clinical updates on phantom limb pain.

INTRODUCTION: Most patients with amputation (up to 80%) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. METHODS: This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. RESULTS: The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. DISCUSSION: Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

Exposure to the thin beauty ideal: Are there subliminal priming effects?

OBJECTIVE: Previous research suggested that exposure to the thin beauty ideal propagated by the media is associated with body dissatisfaction and the development of disordered eating. Given recent suggestions regarding the role of automatic processes, we aimed to enhance our understanding of automatic, unconscious responses to body pictures and the association with the internalization of the thin ideal and the severity of eating disorder symptoms. METHOD: An affective priming task with body pictures of different weight as primes and a normal-weight body picture as target, which had to be evaluated with regard to attractiveness and desirability, was administered to healthy women with either subliminal prime presentation (Experiment 1) or conscious presentation (Experiment 2). RESULTS: Subliminal presentation did not affect the evaluation of the normal-weight target, although strength of evaluative shifts was significantly associated with internalization of the thin ideal. In contrast, the conscious presentation of the ultra-thin prime decreased and of the obese prime increased desirability and attractiveness ratings of the target. DISCUSSION: Prevention strategies focusing on the critical evaluation of the thin ideal are important. Future studies are warranted to enhance our understanding of automatic, unconscious processes in women experiencing eating disorders.

Differential effects of visually induced analgesia and attention depending on the pain stimulation site.

BACKGROUND: The term 'visually induced analgesia' describes a reduced pain perception induced by watching the painful body part as opposed to watching a neutral object. In chronic back pain patients, experimental pain, movement-induced pain and habitual pain can be reduced with visual feedback. Visual feedback can also enhance the effects of both massage treatment and manual therapy. The impact of somatosensory attentional processes remains unclear. METHODS: In the current study, participants received painful electrical stimuli to their thumb and back while being presented with either a real-time video of their thumb or back (factor feedback). In addition, using an oddball paradigm, they had to count the number of deviant stimuli, applied to either their back or thumb (factor attention) and rate the pain intensity. RESULTS: We found a significant main effect for attention with decreased pain ratings during attention. There was no main effect for visual feedback and no significant interaction between visual feedback and attention. Post-hoc tests revealed that the lowest pain intensity ratings were achieved during visual feedback of the back/ thumb and counting at the back/ thumb. CONCLUSION: These data suggest that the modulation of perceived acute pain by visually induced analgesia may be influenced by a simultaneous somatosensory attention task. SIGNIFICANCE: Somatosensory attention reduced experimental pain intensity in the thumb and back in the presence of both congruent and incongruent visual feedback. We found no significant visual feedback effect on the complex interplay between visual feedback and somatosensory attention.

Relationship of prosthesis ownership and phantom limb pain: results of a survey in 2383 limb amputees.

ABSTRACT: Phantom limb pain (PLP) accounts for a significant reduction in quality of life and is difficult to treat. Prosthesis use has been shown to negatively covary with PLP. Recent research on body perception in amputees suggest that prosthesis ownership, defined as the extent to which a prosthesis is experienced as being part of the body rather than an artificial device foreign to the body, might interact with PLP. We used survey data from 2383 unilateral prosthesis-using upper-limb or lower-limb amputees and performed regression analyses to determine the relationship between prosthesis ownership and PLP. To test for specificity, we examined the role of prosthesis ownership also for residual limb pain (RLP) and nonpainful phantom limb sensations (npPLS). Prosthesis ownership was reduced in older participants and higher in lower-limb compared to upper-limb amputees. A longer residual limb and more frequent prosthesis use as well as a longer time since amputation also yielded higher values. Prostheses based on natural principles were associated with higher prosthesis ownership. Phantom limb pain and RLP were lower with higher prosthesis ownership, and RLP but not PLP was lower when prosthesis use was frequent. There were no significant associations for npPLS. The regression results differ in some aspects from those revealed by univariate analyses, emphasizing the importance of multivariate statistical approaches. Our findings provide insights into the interplay of body- and pain-related sensations after amputation, and could help to develop new treatment approaches for both PLP and RLP.

How the unconscious mind controls body movements: Body schema distortion in anorexia nervosa.

OBJECTIVE: Besides all visible somatic manifestations, distorted body representation is a key symptom for anorexia nervosa (AN). Body representation can be divided into a conscious component, body image, and an unconscious action-related one, body schema. As behavioral studies already explored the impact of a distorted body image in AN, we aimed to explore whether distortion also extends into unconscious body schema. This study is the first with an unbiased measurement of the body schema in a homogeneous sample of AN patients. METHOD: Twenty-three patients diagnosed with AN and 23 healthy controls (HC) walked through a door like aperture varying in width. Door width was based on participants shoulder width and ranged from an aperture-to-shoulder-ratio of (A/S) 0.9 to 1.45. Shoulder rotation was measured as indication of perceived body width. To measure the unconscious body schema, we used a cover story pretending to investigate the influence of change of position on retention memory. RESULTS: We found a significantly higher critical A/S for AN than HC, which indicates that AN patients rotate their shoulders for relatively larger door widths than HC, thus unconsciously estimating their body size to be larger than in reality. Additionally, we found a correlation between negative body attribution and overestimation of bodily dimensions. DISCUSSION: As stated by the "allocentric-lock"-hypothesis, AN patients might be locked to a stored representation of their body that cannot be updated and remains at pre-AN conditions. We suggest future AN-therapy to counter body schema alterations by combining cognitive behavioral therapy and virtual reality therapy.

Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective.

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Here we examined if methodological differences in the assessment of cortical representations might explain these findings. We used functional magnetic resonance imaging during a virtual reality movement task, analogous to the classical mirror box task, in twenty amputees with and without PLP and twenty matched healthy controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 and motor cortex (M1) in individually-defined or group-conjoint regions of interest (ROI) (overlap of task-related activation between the groups). We also measured cortical distances between both locations and correlated them with PLP intensity. Amputees compared to controls showed significantly increased activation in M1, S1 and S1M1 unrelated to PLP. Neural activity in M1 was positively related to PLP intensity in amputees with PLP when a group-conjoint ROI was chosen. The location of activation maxima differed between groups in S1 and M1. Cortical distance measures were unrelated to PLP. These findings suggest that sensory and motor maps differentially relate to PLP and that methodological differences might explain discrepant findings in the literature.