Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia

Science ◽  
2017 ◽  
Vol 358 (6359) ◽  
pp. 105-108 ◽  
Author(s):  
A. Tinnermann ◽  
S. Geuter ◽  
C. Sprenger ◽  
J. Finsterbusch ◽  
C. Büchel

Value information about a drug, such as the price tag, can strongly affect its therapeutic effect. We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance. Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia than labeling it as cheap medication. This effect was mediated by neural interactions between cortex, brainstem, and spinal cord. In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia. Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.

2021 ◽  
Author(s):  
JC Motzkin ◽  
J Hiser ◽  
I Carroll ◽  
R Wolf ◽  
MK Baskaya ◽  
...  

AbstractPain is strongly modulated by expectations and beliefs. Research across species indicates that subregions of the ventromedial prefrontal cortex (VMPFC) play a fundamental role in learning and generating predictions about valued outcomes. Consistent with this overarching framework, neuroimaging studies of experimental pain indicate that VMPFC activation tracks expectations of pain relief and statistically mediates expectation-related reductions in responses to painful stimuli across a distributed pain processing network. However, lesion studies in preclinical models and in humans with refractory chronic pain suggest that VMPFC may play a more general role in representing the affective and motivational qualities of pain that contribute to its strong aversive drive. To test whether VMPFC is necessary for pain processing in general, or instead plays a more specific role in the modulation of pain by expectations, we studied responses to experimental heat pain in five adults with bilateral surgical lesions of VMPFC and twenty healthy adults without brain damage.All participants underwent quantitative sensory testing (QST) to characterize pain sensitivity, followed by a pain expectancy task. Participants were instructed that auditory cues would be followed by heat calibrated to elicit low or high pain. Following a conditioning phase, each cue was intermittently paired with a single temperature calibrated to elicit moderate pain. We compared ratings of moderate heat stimuli and subjective expectancy ratings as a function of cue to evaluate whether VMPFC lesions impact cue-based expectancy and expectancy effects on pain intensity and unpleasantness. We also analyzed QST measures to evaluate whether VMPFC lesions were associated with overall shifts in pain sensitivity.Compared to adults without brain damage, individuals with VMPFC lesions reported larger differences in expectations as a function of pain-predictive cues, and stronger cue-based modulation of pain ratings, particularly for ratings of pain unpleasantness. There were no group differences in pain sensitivity, nor in the relationship between pain and autonomic arousal, indicating that the impact of VMPFC lesions is specific to expectancy-based modulation of pain unpleasantness.Our findings suggest that the VMPFC is not essential for basic subjective and physiological responses to painful stimuli. Rather, our findings of significantly enhanced cue- related expectancy effects may suggest that VMPFC plays an important role in updating expectations or integrating sensory information with expectations to guide subjective judgements about pain. Taken together, these results expand our understanding VMPFC’s contribution to pain and highlight the role of VMPFC in integrating cognitive representations with sensory information to yield affective responses.


Author(s):  
Kathryn L. Lovell ◽  
Margaret Z. Jones

Caprine β-mannosidosis, an autosomal recessive defect of glycoprotein catabolism, is associated with a deficiency of tissue and plasma -mannosidase and with tissue accumulation and urinary excretion of oligosaccharides, including the trisaccharide Man(β1-4)GlcNAc(βl-4)GlcNAc and the disaccharide Man(β1-4)GlcNAc. This genetic disorder is evident at birth, with severe neurological deficits including a marked intention tremor, pendular nystagmus, ataxia and inability to stand. Major pathological characteristics described in Nubian goats in Michigan and in Anglo-Nubian goats in New South Wales include widespread cytoplasmic vacuolation in the nervous system and viscera, axonal spheroids, and severe myelin paucity in the brain but not spinal cord or peripheral nerves. Light microscopic examination revealed marked regional variation in the severity of central nervous system myelin deficits, with some brain areas showing nearly complete absence of myelin and other regions characterized by the presence of 25-50% of the control number of myelin sheaths.


Author(s):  
Sinto Robindo ◽  
Melda Rumia Rosmeri Simorangkir

ABSTRACT All aspects of development are very important in a person's life where the development of cognition, affection and psychomotor is well developed in accordance with its development, these three aspects can be said to be good and successful if the three aspects develop well. Like wise with the psychomotor aspect where between gross motor and fine motor are also balanced. Motoric is the development of coordinated body movement control between nerves, brain, and spinal cord (spinal cord or spinal cord). Child's gross motorization can be optimized by improving his motor movement coordination skills through physical activity in the form of coordination of body movements. Like throwing, catching, kicking, running, melopat, and maintaining balance. The condition of a Down Syndrome child who experiences weakness in the ability to think will affect in all aspects of his life. Down syndrome children have problems in cognitive abilities, effective and self-care abilities. This results in them needing special education. Basically, the educational goals that children with Down Syndrome want to achieve are not different from those of education in general. Because Down Syndrome children themselves are born in the midst of society. Keywords: football sports, gross motoric, down syndrome


BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049882
Author(s):  
Jing Nong Liang ◽  
Savanna Budge ◽  
Austin Madriaga ◽  
Kara Meske ◽  
Derrick Nguyenton ◽  
...  

IntroductionReduced neuromuscular control due to altered neurophysiological functions of the central nervous system has been suggested to cause movement deficits in individuals with patellofemoral pain (PFP). However, the underlying neurophysiological measures of brain and spinal cord in this population remain to be poorly understood. The purpose of this systematic review is to evaluate the evidence for altered cortical and spinal cord functions in individuals with PFP.Methods and analysisThe protocol for conducting the review was prepared using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will systematically search the literature that examines cortical and spinal cord functions in individuals with PFP, aged 18–45 years. The studies for cross-sectional, prospective, longitudinal, case–control and randomised control trial designs will be included from the following databases: PubMed (MEDLINE), EMBASE and Web of Science. Only studies published in English prior to 1 February 2021 will be included. The risk of bias and quality assessment will be performed using National Institutes of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We will conduct meta-analysis of the data where appropriate. Narrative synthesis will be taken if a meta-analysis is not possible.Ethics and disseminationThis is a systematic review from the existing literature and does not require ethical approval. The results of this study will be published in a peer-reviewed journal in the field of rehabilitation medicine, sports/orthopaedic medicine or neurology, regardless of the outcome.PROSPERO registration numberCRD42020212128.


2021 ◽  
pp. 102692
Author(s):  
Lijian Zhang ◽  
Francisco R. López-Picón ◽  
Yingqin Jia ◽  
Yao Chen ◽  
Juan Li ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii41-ii41
Author(s):  
Junjie Zhen ◽  
Lei Wen ◽  
Shaoqun Li ◽  
Mingyao Lai ◽  
Changguo Shan ◽  
...  

Abstract BACKGROUND According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D). METHODS The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed. RESULTS A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%). CONCLUSION MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.


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