Liver-Specific Expression of Transcriptionally Active SREBP-1c Is Associated with Fatty Liver and Increased Visceral Fat Mass

The pathogenesis of fatty liver is not understood in detail, but lipid overflow as well as de novo lipogenesis (DNL) seem to be the key points of hepatocyte accumulation of lipids. One key transcription factor in DNL is sterol regulatory element-binding protein (SREBP)-1c. We generated mice with liver-specific over-expression of mature human SREBP-1c under control of the albumin promoter and a liver-specific enhancer (alb-SREBP-1c) to analyze systemic perturbations caused by this distinct alteration. SREBP-1c targets specific genes and causes key enzymes in DNL and lipid metabolism to be up-regulated. The alb-SREBP-1c mice developed hepatic lipid accumulation featuring a fatty liver by the age of 24 weeks under normocaloric nutrition. On a molecular level, clinical parameters and lipid-profiles varied according to the fatty liver phenotype. The desaturation index was increased compared to wild type mice. In liver, fatty acids (FA) were increased by 50% (p<0.01) and lipid composition was shifted to mono unsaturated FA, whereas lipid profile in adipose tissue or serum was not altered. Serum analyses revealed a ∼2-fold (p<0.01) increase in triglycerides and free fatty acids, and a ∼3-fold (p<0.01) increase in insulin levels, indicating insulin resistance; however, no significant cytokine profile alterations have been determined. Interestingly and unexpectedly, mice also developed adipositas with considerably increased visceral adipose tissue, although calorie intake was not different compared to control mice. In conclusion, the alb-SREBP-1c mouse model allowed the elucidation of the systemic impact of SREBP-1c as a central regulator of lipid metabolism in vivo and also demonstrated that the liver is a more active player in metabolic diseases such as visceral obesity and insulin resistance

The rubber hand universe: On the impact of methodological differences in the rubber hand illusion.

Riemer M, Trojan J, Beauchamp M, Fuchs X. The rubber hand universe: On the impact of methodological differences in the rubber hand illusion. Neuroscience and biobehavioral reviews. 2019;104:268-280.The rubber hand illusion (RHI) is a widely applied paradigm to investigate changes in body representations. Extensive scientific interest has produced a great variability in the observed results and many contradictory findings have been reported. Taking into account the numerous variations in the experimental implementation of the RHI, many of these contradictive findings can be reconciled, but to date a thorough analysis of the methodological differences between RHI studies is lacking. Here we summarize and analyse methodological differences between RHI studies. In distinction from other reviews focusing on the integration of findings from various studies, the present paper is devoted to the differences in (i) the experimental setup, (ii) the method used to induce the RHI, (iii) the quantification of its effects, and (iv) aspects of the experimental design and data analysis. This approach will provide a reference frame for the interpretation of previous studies as well as for the design of future studies. Copyright © 2019 Elsevier Ltd. All rights reserved

Body, space and pain

There is growing interest in understanding how the perception of pain (and touch) is influenced by the way we represent our body and the space surrounding it. Recent views argue that pain can only be understood in a larger framework of body perception and action. This attention is driven by accumulating research in experimental and clinical domains, indicating that pain perception depends largely on cognitive factors and multisensory integration. The interest is also boosted by studies on chronic pain conditions suggesting a tight link between body perception and the maintenance of pain. Many aspects remain yet to be elucidated. We welcomed submissions from researchers in cognitive neuroscience and pain to increase our understanding of the interplay among body, space, pain, touch and movement. We aimed to gather insights from different theoretical frameworks and encouraged investigators using a broad range of methods including (but not limited to) behavioural and neuropsychological approaches, imaging techniques, electrophysiology, psychophysiology and TMS to present their results in this Research Topic. In the attempt to go from bench- to bedside we also strongly encouraged submissions from clinicians and physiotherapist whose contribution may help rising some future key questions. Qualitative and phenomenological approaches were also welcome

Synchronous stimulation with light and heat induces body ownership and reduces pain perception.

Cordier L, Fuchs X, Herpertz S, Trojan J, Diers M. Synchronous stimulation with light and heat induces body ownership and reduces pain perception. The journal of pain : official journal of the American Pain Society. 2019.In this study, we investigated whether illusionary body ownership over artificial hands and non-corporeal objects modulates pain perception. Previous research has yielded to mixed results, but has separated painful stimulation used to test pain perception from the stimulation that was used to induce the illusion. Here, we used a variant of the rubber hand illusion (RHI) paradigm and induced the illusion directly via a combination of visual and painful stimuli. We presented heat pain stimuli at the real hand and visual stimuli beneath a rubber hand (part1), or a glass ball (part2). Illusion ratings were higher and pain ratings were lower in the synchronous compared to the asynchronous condition in both parts of the experiment. This study demonstrated the successful induction of a body illusion using a new visual-thermal method with painful stimuli. We showed that the RHI and interestingly also the glass ball has an analgesic effect on the perception of the heat pain stimuli. Our data suggests that induced ownership over artificial limbs but also over non-corporeal objects can reduce the perceived pain perception. This might be mediated via a partial referral of the perceived location of pain or respectively a distribution of pain over two locations. Perspective: This article presents a new visual-thermal method with painful stimuli for the induction of the Rubber Hand Illusion. An illusionary body ownership over artificial hands and non-corporeal has an analgesic effects on the perception of pain. Similar approaches might be useful to alleviate chronic pain, but needs further testing. Copyright © 2019. Published by Elsevier Inc

Prism adaptation contrasts perceptual habituation for repetitive somatosensory stimuli

Prism Adaptation is a non-invasive procedure that requires performing a visuo-motor pointing task while wearing prism goggles inducing a visual displacement of the pointed target. This procedure involves a reorganization of sensorimotor coordination, and induces long-lasting effects on numerous higher-order cognitive functions in healthy volunteers and neglect patients. Prismatic displacement (PD) of the visual field can be induced when prisms are worn but no sensorimotor task is required. In this case, it is unlikely that any subsequent reorganization takes place. The effects of PD are short-lived in the sense that they last until prisms are worn. In this study we aimed, to the best of our knowledge for the first time, at investigating whether PA and PD induce changes in the perception of intensity of experimentally applied tactile and nociceptive stimuli in healthy volunteers. We induced PD (experiment 1), or PA (experiment 2) and asked participants to rate the intensity of nociceptive and non-nociceptive somatosensory stimuli applied to the hand undergoing the visuo-proprioceptive conflict (experiment 1) or adaptation (experiment 2). Our results indicate that: 1) the visuo-proprioceptive conflict induced by PD does not reduce the perceived intensity of the stimuli, 2) PA prevents perceptual habituation for nociceptive and non-nociceptive somatosensory stimuli. Moreover, to investigate the possible underlying mechanisms of the effects of PA we conducted a third experiment in which stimuli were applied both at the adapted and non-adapted hand. We observed that perceptual habituation was prevented for nociceptive and non-nociceptive somatosensory stimuli, for stimuli applied onto both hands. This result suggests that the detention of habituation is probably not merely driven by changes in spatial attention allocation. Taken together, these data indicate that prisms can directly affect the perceived intensity of somatosensory stimuli only when PA is induced

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

Andoh J, Milde C, Diers M, et al. Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective. Scientific reports. 2020;10(1): 11504.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

The prevalence and characteristics of phantom limb pain and non-painful phantom phenomena in a nationwide survey of 3374 unilateral limb amputees.

Diers M, Krumm B, Fuchs X, et al. The prevalence and characteristics of phantom limb pain and non-painful phantom phenomena in a nationwide survey of 3374 unilateral limb amputees. The journal of pain. 2021.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 two 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. Copyright © 2021. Published by Elsevier Inc

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

Fuchs X, Diers M, Trojan J, et al. Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face. European journal of pain. Accepted.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. In this study, we applied QST in 37 unilateral upper-limb amputees (23 with, 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain (PPT), warmth detection (WDT), 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. 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. We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms. This article is protected by copyright. All rights reserved