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      Appearance of fetal pain could be associated with maturation of the mesodiencephalic structures

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          Fetal pain remains a controversial subject both in terms of recognizing its existence and the time-frame within which it appears. This article investigates the hypothesis that pain perception during development is not related to any determined structures of the central nervous system (CNS), on the contrary, the process of perception could be made with any structure satisfying conditions that the perception of pain is the organization, identification, and interpretation of sensory information in order to represent and understand the environment. According to this definition, chronic decerebrate and decorticate experimental animals, anencephalic, and hydranencephalic patients demonstrate that the basic, most general, appropriate interaction with the environment can be achieved with a functional mesodiencephalon (brain stem, and diencephalon) as the hierarchically highest structure of the CNS during development. In intact fetuses, this structure shows signs of sufficient maturation starting from the 15th week of gestation. Bearing in mind the dominant role of the reticular formation of the brain stem, which is marked by a wide divergence of afferent information, a sense of pain transmitted through it is diffuse and can dominate the overall perception of the fetus. The threshold for tactile stimuli is lower at earlier stages of gestation. The pain inhibition mechanisms are not sufficiently developed during intrauterine development, which is another factor that leads to increased intensity of pain in the fetus. As a conclusion it could be proposed that the fetus is exposed to rudimentary painful stimuli starting from the 15 th gestation week and that it is extremely sensitive to painful stimuli.

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          Pain and its effects in the human neonate and fetus.

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            Effect of neonatal circumcision on pain response during subsequent routine vaccination.

            Preliminary studies suggested that pain experienced by infants in the neonatal period may have long-lasting effects on future infant behaviour. The objectives of this study were to find out whether neonatal circumcision altered pain response at 4-month or 6-month vaccination compared with the response in uncircumcised infants, and whether pretreatment of circumcision pain with lidocaine-prilocaine cream (Emla) affects the subsequent vaccination response. We used a prospective cohort design to study 87 infants. The infants formed three groups--uncircumcised infants, and infants who had been randomly assigned Emla or placebo in a previous clinical trial to assess the efficacy of Emla cream as pretreatment for pain in neonatal circumcision. Infants were videotaped during vaccination done at the primary care physician's clinic. Videotapes were scored without knowledge of circumcision or treatment status by a research assistant who had been trained to measure infant facial action, cry duration, and visual analogue scale pain scores. Birth characteristics and infant characteristics at the time of vaccination, including age and temperament scores, did not differ significantly among groups. Multivariate ANOVA revealed a significant group effect (p < 0.001) in difference (vaccination minus baseline) values for percentage facial action, percentage cry time, and visual analogue scale pain scores. Univariate ANOVAs were significant for all outcome measures (p < 0.05): infants circumcised with placebo had higher difference scores than uncircumcised infants for percentage facial action (136.9 vs 77.5%), percentage cry duration (53.8 vs 24.7%), and visual analogue scale pain scores (5.1 vs 3.1 cm). There was a significant linear trend on all outcome measures, showing increasing pain scores from uncircumcised infants, to those circumcised with Emla, to those circumcised with placebo. Circumcised infants showed a stronger pain response to subsequent routine vaccination than uncircumcised infants. Among the circumcised group, preoperative treatment with Emla attenuated the pain response to vaccination. We recommend treatment to prevent neonatal circumcision pain.
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              Central thalamic contributions to arousal regulation and neurological disorders of consciousness.

               Gordon Schiff (2007)
              This review focuses on the contributions of the central thalamus to normal mechanisms of arousal regulation and to neurological disorders of consciousness. Forebrain arousal is regulated by ascending influences from brainstem/basal forebrain neuronal populations ("arousal systems") and control signals descending from frontal cortical systems. These subcortical and cortical systems have converging projections to the central thalamus that emphasize their role in maintaining organized behavior during wakefulness. Central thalamic neurons appear to be specialized both anatomically and physiologically to support distributed network activity that maintains neuronal firing patterns across long-range cortico-cortical pathways and within cortico-striatopallidal-thalamocortical loop connections. Recruitment of central thalamic neurons occurs in response to increasing cognitive demand, stress, fatigue, and other perturbations that reduce behavioral performance. In addition, the central thalamus receives projections from brainstem pathways evolved to rapidly generate brief shifts of arousal associated with the appearance of salient stimuli across different sensory modalities. Through activation of the central thalamus, neurons across the cerebral cortex and striatum can be depolarized and their activity patterns selectively gated by descending or ascending signals related to premotor attention and alerting stimuli. Direct injury to the central thalamus or prominent deafferentation of these neurons as a result of complex, multifocal, brain insults are both associated with severe impairment of forebrain functional integration and arousal regulation. Interventions targeting neurons within the central thalamus may lead to rational therapeutic approaches to the treatment of impaired arousal regulation following nonprogressive brain injuries. A model accounting for present therapeutic strategies is proposed.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                11 November 2016
                : 9
                : 1031-1038
                [1 ]Department of Neurology, Faculty of Medicine Novi Sad, University of Novi Sad
                [2 ]Department of Obstetrics and Gynecology, Faculty of Medicine Novi Sad, University of Novi Sad
                [3 ]Department of Histology and Embryology, Faculty of Medicine Novi Sad, University of Novi Sad
                [4 ]Department of Developmental Neurology and Epilepsy, Institute for Child and Youth Health Care of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
                [5 ]School of Applied Psychology, Institute Humans in Complex Systems, Olten, Switzerland
                [6 ]Department of Orthopaedics and Traumatology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, Greece
                Author notes
                Correspondence: Slobodan Sekulic, Department of Neurology, Clinical Center of Vojvodina, Hajduk Veljkova 1-7, 21000 Novi Sad, Serbia, Tel +381 6 4388 6715, Email slobodan.sekulic@ 123456mf.uns.ac.rs
                © 2016 Sekulic et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.


                Anesthesiology & Pain management

                pain, fetus, perception, brain stem, thalamus


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