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      The Hypnotic Analgesia Suggestion Mitigated the Effect of the Transcranial Direct Current Stimulation on the Descending Pain Modulatory System: A Proof of Concept Study

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          Abstract

          Objective

          We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF).

          Materials and Methods

          Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA.

          Results

          A generalized linear model revealed a significant main effect for the intervention group (P <0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was −0.25 (0.43). The (Δ) pain score on NPS (0–10) during CPM-test in the other three groups was a-tDCS=−0.54 (0.41), HS −0.01 (0.41) and s-tDCS/HS=−0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo.

          Conclusion

          These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT.

          Clinical Trial Registration

          www.ClinicalTrials.gov , identifier NCT03744897.

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          Most cited references 54

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          Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

          In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.
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            Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat.

            (1) Sixty-eight convergent dorsal horn neurones have been recorded at the lumbar level in anaesthetized intact rats. All cells received prominent A alpha and C fibre afferents and correspondingly could be activated by high and low threshold stimuli applied to the peripheral excitatory receptive field. (2) The activity of 67/68 of these neurones was powerfully inhibited by noxious stimuli applied to various parts of the body. Since non-noxious stimuli were ineffective in this respect, the term "diffuse noxious inhibitory controls" (DNIC) is proposed. (3) DNIC could be evoked by noxious pinch applied to the tail, the contralateral hind paw, the forepaws, the ears and the muzzle; the most effective areas were the tail and muzzle. Noxious heat applied to and transcutaneous electrical stimulation of the tail were extemely effective in eliciting DNIC as was the intraperitoneal injection of bradykinin. (4) DNIC strongly depressed by 60-100% both the C fibre response following suprathreshold transcutaneous electrical stimulation and the responses to noxious radiant heat. (5) The spontaneous activity and the responses to low threshold afferents induced either by A alpha threshold electrical or natural stimulation were also powerfully inhibited. (6) In the majority of cases, long lasting post-effects directly related to the duration of conditioning painful stimulus were observed.
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              Cerebral location of international 10-20 system electrode placement.

              We employed CT scanning to correlate scalp markers placed according to the international 10-20 system with underlying cerebral structures. Subjects were 12 normal volunteers. Measurements included assessment for cranial asymmetry to determine the effect of skull asymmetry on cortical location of electrodes. Results were correlated with the cortical histological map of Brodmann. Primary cortical locations agree well with previously published data and provide cortical localization in greater detail than previous studies. Variability of cortical electrode location was substantial in some cases and not related to cranial asymmetry. The results indicate that CT scanning or other neuroimaging techniques which reveal detailed cerebral anatomy would be potentially highly useful in defining the generators of electrocerebral potentials recorded from the scalp.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                16 September 2020
                2020
                : 13
                : 2297-2311
                Affiliations
                [1 ]Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal Do Rio Grande Do Sul (UFRGS) , Porto Alegre, Brazil
                [2 ]Laboratory of Pain and Neuromodulation at Hospital De Clínicas De Porto Alegre (HCPA) , Porto Alegre, Brazil
                [3 ]Psychology Department, Universidad Catolica De Cuenca, UCACUE , Cuenca, Ecuador
                [4 ]Department of Pharmacology, Institute of Health Sciences (ICBS), Universidade Federal Do Rio Grande Do Sul (UFRGS) , Porto Alegre, Brazil
                [5 ]Pharmacology of Pain and Neuromodulation: Pre-Clinical Investigations Research Group, Universidade Federal Do Rio Grande Do Sul (UFRGS) , Porto Alegre, Brazil
                [6 ]Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, USA
                Author notes
                Correspondence: Wolnei Caumo Fax + (55) 51- 3359.8083 Email wcaumo@hcpa.edu.br
                Article
                253747
                10.2147/JPR.S253747
                7502396
                © 2020 Beltran Serrano 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 4, Tables: 15, References: 67, Pages: 15
                Funding
                Funded by: Brazilian agencies, Committee for the Development of Higher Education Personnel – CAPES - PROEX;
                Funded by: Postgraduate Research Group at the Hospital de Clínicas de Porto Alegre – FIPE HCPA;
                Funded by: Brazilian Innovation Agency (FINEP) process number - 1245/13 (Dr. I.L.S. Torres, Dr. W. Caumo);
                Funded by: National Council for Scientific and Technological Development-CNPq (Torres, I.L.S. 302345/2011-6 and Caumo, W. WC-301256/2013-6);
                Brazilian agencies, Committee for the Development of Higher Education Personnel – CAPES - PROEX to material support. Postgraduate Research Group at the Hospital de Clínicas de Porto Alegre – FIPE HCPA (material support - 16-0635). Brazilian Innovation Agency (FINEP) process number - 1245/13 (Dr. I.L.S. Torres, Dr. W. Caumo). Research grant: National Council for Scientific and Technological Development-CNPq (Torres, I.L.S. 302345/2011-6 and Caumo, W. WC-301256/2013-6).
                Categories
                Clinical Trial Report

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