Modulation Of Experimental Prolonged Pain and Sensitization Using High-Definition Transcranial Direct Current Stimulation: A Double-Blind, Sham-Controlled Study

Kold, Sebastian; Graven‐Nielsen, Thomas

doi:10.1016/j.jpain.2022.01.012

Cited by 4 publications

(7 citation statements)

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“…A possible explanation is that the experimental pain provocation perturbed the central nervous system, rendering the pain groups more susceptible to modulation than the non‐pain groups (Antal et al, 2008 ; Thapa et al, 2018 ; Wittkopf et al, 2021 ). This theory is in line with previous findings from experimental studies (Horvath et al, 2015 ; Kold & Graven‐Nielsen, 2021 , 2022 ), and is supported by a meta‐review examining the modulatory effect of tDCS on sensory thresholds, which showed that the modulatory effect is larger in pain patients with sensitized central nervous systems than healthy subjects (Giannoni‐Luza et al, 2020 ).…”

Section: Discussionsupporting

confidence: 89%

“…All participants received written and verbal information about the study and signed a consent form before the first experimental session. The study was performed according to the Helsinki Declaration, approved by the North Denmark Region Committee on Health Research Ethics (VN‐20180085), and was registered at http://clinicaltrials.gov (NCT04650048 (Kold & Graven‐Nielsen, 2022) and NCT04165876 (Kold & Graven‐Nielsen, 2021)).…”

Section: Methodsmentioning

confidence: 99%

“…Eighty healthy participants (38 females) aged 18–55 years were included in this study conducted at Center for Neuroplasticity of Pain (CNAP), Aalborg University, Denmark, between 18/12/2018 and 21/12/2020. Participants were originally enrolled in two studies focusing on static quantitative sensory testing (single‐point mechanical and thermal thresholds) following HD‐tDCS with (Kold & Graven‐Nielsen, 2021 ) and without (Kold & Graven‐Nielsen, 2022 ) prolonged experimental pain. The two studies followed identical inclusion and exclusion criteria and were conducted in the same test facility and by the same investigator that was trained in the assessment and tDCS methods.…”

Section: Methodsmentioning

confidence: 99%

“…The first forty subjects (Kold & Graven‐Nielsen, 2021 ) were randomly assigned to either the Sham‐tDCS group ( N = 20) or active‐tDCS group ( N = 20). The subsequent forty subjects had tonic experimental pain induced (Kold & Graven‐Nielsen, 2022 ) and were randomly assigned to the Pain‐Sham‐tDCS group ( N = 20) or Pain‐Active‐tDCS group ( N = 20). Randomization was done by a third party that prior to the experiment, had assigned the subject IDs to the four corresponding groups.…”

Section: Methodsmentioning

confidence: 99%

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Modulation of central pain mechanisms using high‐definition transcranial direct current stimulation: A double‐blind, sham‐controlled study

Kold

Graven‐Nielsen

2022

European Journal of Pain

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Background:The use of high-definition transcranial direct current stimulation (HD-tDCS) has shown analgesic effects in some chronic pain patients, but limited anti-nociceptive effects in healthy asymptomatic subjects. Methods: This double-blinded sham-controlled study assessed the effects of HD-tDCS applied on three consecutive days on central pain mechanisms in healthy participants with (N = 40) and without (N = 40) prolonged experimental pain induced by intramuscular injection of nerve growth factor into the right hand on Day 1. Participants were randomly assigned to Sham-tDCS (N = 20 with pain, N = 20 without) or Active-tDCS (N = 20 with pain, N = 20 without) targeting simultaneously the primary motor cortex and dorsolateral prefrontal cortex for 20 min with 2 mA stimulation intensity. Central pain mechanisms were assessed by cuff algometry on the legs measuring pressure pain sensitivity, temporal summation of pain (TSP) and conditioned pain modulation (CPM), at baseline and after HD-tDCS on Day 2 and Day 3. Based on subject's assessment of received HD-tDCS (sham or active), they were effectively blinded. Results: Compared with Sham-tDCS, Active-tDCS did not significantly reduce the average NGF-induced pain intensity. Tonic pain-induced temporal summation at Day 2 and Day 3 was significantly lower in the NGF-pain group under Active-tDCS compared to the pain group with Sham-tDCS (p ≤ 0.05). No significant differences were found in the cuff pressure pain detection/tolerance thresholds or CPM effect across the 3 days of HD-tDCS in any of the four groups. Conclusion: HD-tDCS reduced the facilitation of TSP caused by tonic pain suggesting that efficacy of HD-tDCS might depend on the presence of sensitized central pain mechanisms.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of central pain mechanisms using high‐definition transcranial direct current stimulation: A double‐blind, sham‐controlled study

Kold

Graven‐Nielsen

2022

European Journal of Pain

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“…5). 4,5,7,28,36,45,46,59,68,90,122,152,153,170,199,209,213,229,230,234,235,257,262,269 Similarly, injection of NGF into the infrapatellar fat did not evoke pain at injection but rather hyperalgesia after 1 day. 165 More intense NGF-induced muscle pain and hyperalgesia have been reported in women compared with men, and expression of N-methyl-D-aspartate receptors on peripheral nerve fibres may partly explain the long-term hyperalgesia and pain, particularly in women.…”

Section: Introductionmentioning

confidence: 96%

Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Graven‐Nielsen

2022

Pain

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Effects of High-Definition Transcranial Direct Current Stimulation Targeting the Anterior Cingulate Cortex on the Pain Thresholds: A Randomized Controlled Trial

Xiong

Cao

et al. 2022

Pain Medicine

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Background The majority of existing clinical studies used active transcranial direct current stimulation (tDCS) over the superficial areas of pain neuromatrix to regulate pain, with conflicting results. Nevertheless, few studies have investigated the effect of tDCS on pain thresholds by focusing on targets in deep parts of the pain neuromatrix. Methods This study applied single session of high-definition tDCS (HD-tDCS) targeting the anterior cingulate cortex (ACC) with a parallel and sham-controlled design, to compare the antinociceptive effects in healthy individuals through assessing changes in pain thresholds. Sixty-six (mean age, 20.5 ± 2.4) female individuals were randomly allocated into the anodal, cathodal, or sham HD-tDCS groups. The primary outcome of the study was pain thresholds (pressure pain threshold, heat pain threshold, and cold pain threshold), which were evaluated before and after stimulation by the quantitative sensory tests. Results Only cathodal HD-tDCS targeting the ACC significantly increased heat pain threshold (p < 0.05) and pressure pain threshold (p < 0.01) in healthy individuals compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain threshold. Furthermore, no statistically significant difference was found in pain thresholds between anodal vs. sham HD-tDCS (p > 0.38). Independent of HD-tDCS protocols, the positive and negative affective schedule scores were decreased immediately after stimulation compared with baseline. Conclusions The present study has found that cathodal HD-tDCS targeting the ACC provided a strong antinociceptive effect (increase in pain threshold), demonstrating a positive biological effect of HD-tDCS. Clinical Trials Registration An RCT was carried out at Shanghai University of Sport, China, from December 2021 to March 2022. Trial registration: ChiCTR2100053531. Registered 24 November 2021, http://www.chictr.org.cn/index.aspx.

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Modulation Of Experimental Prolonged Pain and Sensitization Using High-Definition Transcranial Direct Current Stimulation: A Double-Blind, Sham-Controlled Study

Cited by 4 publications

References 76 publications

Modulation of central pain mechanisms using high‐definition transcranial direct current stimulation: A double‐blind, sham‐controlled study

Modulation of central pain mechanisms using high‐definition transcranial direct current stimulation: A double‐blind, sham‐controlled study

Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Effects of High-Definition Transcranial Direct Current Stimulation Targeting the Anterior Cingulate Cortex on the Pain Thresholds: A Randomized Controlled Trial

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