High-definition transcranial direct current stimulation (HD-tDCS) of brain areas related to pain processing may provide analgesic effects evident in the sensory detection and pain thresholds.The somatosensory sensitivity was assessed following HD-tDCS targeting the primary motor cortex (M1) and/or the dorsolateral prefrontal cortex (DLPFC). Eighty-one (40 females) subjects were randomly assigned to one of four anodal HD-tDCS protocols (20 min) applied on three consecutive days: Sham-tDCS, DLPFC-tDCS, M1-tDCS, and DLPFC&M1-tDCS (simultaneous tDCS of DLPFC and M1). Subjects and experimenter were blinded to the tDCS protocols. The somatosensory sensitivity were assessed each day, before and after each tDCS by detection and pain thresholds to thermal and mechanical skin stimulation, vibration detection thresholds, and pressureby the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited. 2021 4 pain thresholds. Subjects were effectively blinded to the protocol, with no significant difference in rates of whether they received real or placebo tDCS between the four groups. Compared with the Sham-tDCS, none of the active HD-tDCS protocols caused significant changes in detection or pain thresholds. Independent of tDCS protocols, pain and detection thresholds except vibration detection were increased immediately after the first tDCS protocol compared with baseline (P <0.05).Overall, the active stimulation protocols were not able to induce significant modulation of the somatosensory thresholds in this healthy population compared to sham-tDCS. Unrelated to the HD-tDCS protocol a decreased sensitivity was found after the first intervention, indicating a placebo effect or possibly habituation to the QST assessments. These findings add to the increasing literature of null-findings in the modulatory effects of HD-tDCS on the healthy somatosensory system.

Objectives Anodal transcranial direct current stimulation (tDCS) of primary motor cortex (M1) and cathodal of the primary sensory cortex (S1) have previously shown to modulate the sensory thresholds when administered with the reference electrode located over the contralateral supraorbital area (SO). Combining the two stimulation paradigms into one with simultaneous stimulation of the two brain areas (M1 + S1 − tDCS) may result in a synergistic effect inducing a prominent neuromodulation, noticeable in the pain thresholds. The aim of this study is to assess the efficacy of the novel M1 + S1 − tDCS montage compared to sham-stimulation in modulating the pain thresholds in healthy adults. Methods Thirty-nine (20 males) subjects were randomly assigned to either receiving 20 min. active M1 + S1 − tDCS or sham tDCS in a double-blinded single session study. Thermal and mechanical pain thresholds were assessed before and after the intervention. Results There were no significant differences in the pain thresholds within either group, or between the M1 + S1 − tDCS group and the Sham-tDCS group (p>0.05), indicating that the intervention was ineffective in inducing a neuromodulation of the somatosensory system. Conclusions Experimental investigations of novel tDCS electrode montages, that are scientifically based on existing studies or computational modelling, are essential to establish better tDCS protocols. Here simultaneous transcranial direct current stimulation of the primary motor cortex and primary sensory cortex showed no effect on the pain thresholds of the neck musculature in healthy subjects. This tDCS montage may have been ineffective due to how the electrical field reaches the targeted neurons, or may have been limited by the design of a single tDCS administration. The study adds to the existing literature of the studies investigating effects of new tDCS montages with the aim of establishing novel non-invasive brain stimulation interventions for chronic neck pain rehabilitation. North Denmark Region Committee on Health Research Ethics (VN-20180085) ClinicalTrials.gov (NCT04658485).

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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Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception. Using a Pavlovian-learning task, we investigated the influence of prior expectations on the belief about the varying strength of association between a painful electrical cutaneous stimulus and a visual cue in healthy subjects (N = 70). The belief in cue-pain associations was examined with computational modelling using a Hierarchical Gaussian Filter (HGF). Prior weighting estimates in the HGF model were compared with the established measures of conditioned pain modulation (CPM) and temporal summation of pain (TSP) assessed by cuff algometry. Subsequent HGF-modelling and estimation of the influence of prior beliefs on perception showed that 70% of subjects had a higher reliance on nociceptive input during perception of acute pain stimuli, whereas 30% showed a stronger weighting of prior expectations over sensory evidence. There was no association between prior weighting estimates and CPM or TSP. The data demonstrates relevant individual differences in prior weighting and suggests an importance of top-down cognitive processes on pain perception. Our new psychophysical testing paradigm provides a method to identify individuals with traits suggesting greater reliance on prior expectations in pain perception, which may be a risk factor for developing chronic pain and may be differentially responsive to learning-based interventions.

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