Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report
Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100885/ |
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pubmed-4100885 |
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pubmed-41008852014-07-18 Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report DosSantos, Marcos F. Martikainen, Ilkka K. Nascimento, Thiago D. Love, Tiffany M. DeBoer, Misty D. Schambra, Heidi M. Bikson, Marom Zubieta, Jon-Kar DaSilva, Alexandre F. Research Article Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET) scans with [11C]carfentanil, a selective μ-opioid receptor (MOR) radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND) - one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA) tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG), precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS. Public Library of Science 2014-07-16 /pmc/articles/PMC4100885/ /pubmed/25029273 http://dx.doi.org/10.1371/journal.pone.0102350 Text en © 2014 DosSantos et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
DosSantos, Marcos F. Martikainen, Ilkka K. Nascimento, Thiago D. Love, Tiffany M. DeBoer, Misty D. Schambra, Heidi M. Bikson, Marom Zubieta, Jon-Kar DaSilva, Alexandre F. |
| spellingShingle |
DosSantos, Marcos F. Martikainen, Ilkka K. Nascimento, Thiago D. Love, Tiffany M. DeBoer, Misty D. Schambra, Heidi M. Bikson, Marom Zubieta, Jon-Kar DaSilva, Alexandre F. Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| author_facet |
DosSantos, Marcos F. Martikainen, Ilkka K. Nascimento, Thiago D. Love, Tiffany M. DeBoer, Misty D. Schambra, Heidi M. Bikson, Marom Zubieta, Jon-Kar DaSilva, Alexandre F. |
| author_sort |
DosSantos, Marcos F. |
| title |
Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| title_short |
Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| title_full |
Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| title_fullStr |
Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| title_full_unstemmed |
Building up Analgesia in Humans via the Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A Preliminary Report |
| title_sort |
building up analgesia in humans via the endogenous μ-opioid system by combining placebo and active tdcs: a preliminary report |
| description |
Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET) scans with [11C]carfentanil, a selective μ-opioid receptor (MOR) radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND) - one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA) tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG), precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100885/ |
| _version_ |
1613114783182094336 |