Effect of dry-electrode-based transcranial direct current stimulation on chronic low back pain and low back muscle activities: A double-blind sham-controlled study

Abstract

Background:

Dry-electrode-based transcranial direct current stimulation is a new type of non-invasive brain stimulation system which relieves chronic low back pain and improves related muscle movement, in a way that overcomes the drawback of conventional systems.

Objective:

To investigate the effectiveness of dry-electrode-based transcranial direct current stimulation in relieving chronic low back pain and altering pain-related low back muscles movement, by using pain assessment tool and surface electromyographic topography.

Methods:

We conducted a prospective, double-blind, randomized, sham-controlled study. 60 patients with non-specific chronic low back pain were randomly and evenly allocated into tDCS and sham groups. Each group accepted a single 20-minute stimulation at 2 mA on the primary motor cortex. Numeric rating scale for pain intensity assessment and root-mean-square difference parameter from surface electromyographic topography were measured before and after stimulation. The current direction in brain using finite element method was simulated to verify the current distribution under dry stimulation electrode.

Results:

After stimulation, the pain intensity in the tDCS group significantly decreased, while it did not show evident change in the sham group. However, change of root-mean-square difference parameters between tDCS and sham groups showed no significant difference. Simulation results based on finite element method showed most of current focused on primary motor cortex while peak value of current density was 0.225 A/m².

Conclusions:

Dry-electrode-based transcranial direct current stimulation can lower pain perception in patients with chronic low back pain. The analgesic mechanism can affect the top-down modulation pathway of pain.

Keywords

Pain measurement finite element analysis analgesia electrodes

1 Introduction

Chronic low back pain (CLBP) is a common disease (Balagué, Mannion, Pellisé, & Cedraschi, 2011). Due to its complicated etiology, the treatments that are currently available (i.e. physiotherapy, occupational therapy, cognitive-behavioral therapy) cannot cure it, therefore most patients often have to suffer from it throughout their lifespan (Balagué et al., 2011; Ferguson, 2009; KS Rucker, 2001).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique (F. Fregni et al., 2015). According to recent studies on tDCS, this technique showed the potential to be applied to various fields, such as cognitive enhancement for healthy people, improvement of upper limb function after stroke, treatment of schizophrenia, depression, and pain, as well as treatment of memory deficits seen in Parkinson’s disease and Alzheimer’s disease (Berlim, Van den Eynde, & Daskalakis, 2013; Flöel, 2014; Kang, Summers, & Cauraugh, 2016; Mervis, Capizzi, Boroda, & MacDonald, 2017; Nitsche, Boggio, Fregni, & Pascual-Leone, 2009; Tedesco Triccas et al., 2016; Villamar et al., 2013). Regarding to the study about the effect of tDCS on pain, it showed that the anodal stimulation of primary motor cortex (M1) by tDCS is effective in relieving neuropathic pain, fibromyalgia, and phantom pain (Bolognini et al., 2015; Ngernyam et al., 2015; Villamar et al., 2013). Some researchers also have tried to investigate the effect of tDCS on CLBP. However, there is no consistent conclusion. O’Connell et al. (O’Connell et al., 2013) and Luedtke et al. (Luedtke et al., 2015) found that there was no significant difference in the pain intensity after stimulation between tDCS and sham group, whereas Schabrun et al. (Schabrun, Jones, Elgueta Cancino, & Hodges, 2014) found that not only the anodal tDCS on M1 but also the peripheral electrical stimulation (PES) can significantly reduce the pain. The inconsistency of the conclusions in other researches can be attributed to various possible reasons. Firstly, both of the studies used large 35 cm² (5×7 cm) saline-soaked surface sponge electrodes to deliver the direct current. It was difficult to assure the feasibility of the focalized and stable stimulation of target regions, because the saline spreading or dripping on the scalp might guide current flow in undesirable and unpredictable directions and also caused change of current intensity (Brunoni et al., 2012; DaSilva et al., 2015; Horvath, Carter, & Forte, 2014). A second possible factor is the low current intensities reaching cortex and high interindividual variability (Hannah, Iacovou, & Rothwell, 2019; Li, Uehara, & Hanakawa, 2015). In order to solve these problems, some researchers have been trying to develop new types of stimulation electrode (e.g., dry tDCS electrode, High-definition tDCS electrode) (DaSilva et al., 2011; Kuo et al., 2013; Villamar et al., 2013; Wongsarnpigoon, Joseph, Rubin, & Sakai, 2013) to replace the conventional surface sponge electrode. Among all of the new types of electrodes, the focus of our study is the dry-electrode-based tDCS.

The evaluation of the effect of tDCS on CLBP patients was based on the measurement of the change in pain intensity. The measurements most frequently used to measure pain intensity are Numeric Rating Scale (NRS), Visual Analogue Scale (VAS) and Pain Severity subscale of the Brief Pain Inventory (BPI-PS) (Chiarotto et al., 2019; Froud et al., 2016). Among these measurements, VAS was less understandable for patients especially the elderly ones, and BPI-PS was harder to administer than other instruments (Chiarotto et al., 2018). Therefore, NRS was clearly preferred by researchers, clinicians and patients (Chapman et al., 2011; Chiarotto et al., 2018; Chiarotto, Terwee, & Ostelo, 2016). We also adopted NRS to measure the CLBP in this study.

Apart from pain intensity, another important factor to evaluate CLBP is the low back muscle activities. A new objective tool to thoroughly evaluate these activities is dynamic surface electromyographic (sEMG) topography (Hu, Kwok, Yuk-Hang Tse, & Dip-Kei Luk, 2014; Hu, Mak, & Luk, 2009; Hu, Siu, Mak, & Luk, 2010; Jiang, Luk, & Hu, 2017; Mak, Hu, Cheng, et al., 2010; Mak, Hu, & Luk, 2010). So we adopted both NRS and sEMG topography in this study.

By adopting NRS to measure pain intensity, the primary aim of this study was to investigate whether dry-electrode-based tDCS can relieve CLBP. As well, via sEMG topography, we aimed to investigate whether dry-electrode-based tDCS can alter pain-related low back muscle activities.

2 Methods

2.1 Trial design

A prospective, double-blind, randomized, sham-controlled design was used in this study. There were two tDCS program: 1) real tDCS; 2) sham tDCS. Each patient with non-specific LBP received a single session of real/sham tDCS program in a random order while the duration of the program was 20 minutes. Each one was randomly assigned to either tDCS group or sham group using a random number table with an allocation ratio of 1 : 1. The random number table was concealed in consecutively numbered, sealed opaque envelopes. An investigator not involved in recruitment, treatment and assessment provided the envelope to the treating physician who would reveal group allocation. The pain intensity (NRS scale) and low back muscle activity (sEMG topography) was assessed before and after the tDCS program. To avoid bias, both the patients and the assessor were blinded to the intervention status (i.e., real or sham stimulation). Besides, a well-trained orthopaedic surgeon was asked to perform clinical assessments.

2.2 Participants

60 outpatients with non-specific LBP were recruited in the University Hospital. A well-trained orthopaedic surgeon justified whether the LBP is specific or non-specific according to the radiological assessment (e.g., X-ray, computed tomography, or magnetic resonance imaging) and common-used clinical diagnosis (e.g., extension excises). All patients had a history of nonspecific LBP for more than 3 months (27.5±47.6) and were aged from 18 years to 65 years with current pain intensity no less than 3 on an 11-point NRS scale (4.9±1.8). The exclusion criteria include evidence of spinal deficits, a history of any back/brain surgeries, a history of seizures, a family history of epilepsy, a history of loss of consciousness >15 min, implanted medical devices, metal objects in head, known intracranial growths or tumors, known neurological disease, identifiable psychotic illness or other mental illness, pregnant, any open wounds on the scalp and/or face, analgesic or anti-inflammatory medication in the last month or had received treatment from a health professional in the last month. To establish the normal low back muscle activity, a control group of 45 healthy subjects (mean age 34±7.7 years, 24 males and 21 females) were collected from a database of our previous study. Each participant signed the written informed consent before the experiment, while the procedures for this study were approved by the Institutional Ethics Committee and conformed to the Declaration of Helsinki. The trial was also registered in the ClinicalTrials.gov (NCT03511404).

2.3 Interventions

A battery-driven direct current stimulator was used to deliver constant current (0–4 mA) via two surface dry electrodes, see Fig. 1A (Jiang et al., 2018). The anode electrode (round, diameter: 1 cm) consisted of a group of conductive metal spring pins, while the cathode electrode (round, diameter: 4 cm) was a conductive sheet metal. In order to make the cathode electrode fully touch the skin and deliver current to the patient more comfortable, we attached a conductive and sticky film to the surface of the cathode electrode (conductive sheet metal). If the pain was predominantly on 1 side of the patient’s back, the contralateral hemisphere was stimulated, otherwise, the hemisphere contralateral to the patient’s self-nominated dominant hand was stimulated. There are several reasons why we applied this kind of stimulation method. Firstly, to stimulate the left/right M1, instead of central M1, is a common-used protocol for tDCS on pain (e.g., central pain, low back pain, fibromyalgia) (Fregni, Boggio, et al., 2006; Fregni, Gimenes, et al., 2006; Bolognini et al., 2015; Luedtke et al., 2015; O’Connell et al., 2013; Schabrun et al., 2014; Villamar et al., 2013). Secondly, one pathological explanation for the tDCS on pain is that the M1 stimulation can induce widespread changes in the activity of cortical areas and indeed change the activity of the contralateral motor cortex (Lang et al., 2005). Therefore, the unilateral tDCS might lead to the pain relief for patients with bilateral pain. Finally, another pathological explanation is that the extraordinary balance and organization between left and right hemisphere results in the chronic pain (Morishita & Inoue, 2016). Then by activating one side of the hemisphere to rebalance and reorganize the brain network could relieve the chronic pain. Because the hemisphere corresponding to the dominant hand always have stronger activity in the healthy subjects, it is potential to relieve CLBP by activating this hemisphere in the CLBP patients while there is no predominant side of pain. Thus, in this study, for patients in the tDCS group, the anode dry electrode was placed over the C3/C4 position (using the international 10/20 electroencephalography system which was commonly used in tDCS electrodes placement), while the cathode dry electrode was attached over the contralateral supraorbital area (Fig. 1B). In this group, a constant current of 2 mA was delivered for 20 minutes with a 10-second ramp up phase in the beginning by switching on the knob of stimulator and a 10-second ramp down phase in the end by switching off the knob. Meanwhile, the patients in the sham group received the sham stimulation for 20 minutes with the same position for real stimulation. In this sham group, we turned on and off the stimulator with a 10-second ramp up and 10-second ramp down of stimulation current in the beginning and then repeated this procedure in the end. Thus, the patients could feel the itching sensation only in the beginning and end so that they could hardly judge the received stimulation mode. The tDCS system in this study was still investigational.

Fig. 1

tDCS system with dry electrodes. (A) Dry electrodes and a conductive and sticky gel. (B) Electrode positioning used for primary motor cortex stimulation.

2.4 Outcomes

2.4.1 Primary outcomes

Before and after the stimulation program, each patient finished a questionnaire called 11-point NRS for LBP assessment (Hjermstad et al., 2011; Ostelo & de Vet, 2005). The range of NRS was from 0 (no pain at that moment) to 10 (worst imaginable pain at that moment).

2.4.2 Secondary outcomes

In order to construct the sEMG topography, the sEMG signal from participant’s low back muscles needed to be collected. Before collecting the signal, we firstly cleaned the skin of low back muscles with alcohol to keep the impedance lower than 10 kΩ. Then we evenly attached 3×7 array of electrodes (Ag/AgCl, diameter: 1.5 cm) to the surface of low back muscles (L2 to L5) (Fig. 2A) (Hu et al., 2014; Hu et al., 2009; Hu et al., 2010; Jiang et al., 2017; Mak, Hu, Cheng, et al., 2010; Mak, Hu, & Luk, 2010). Sixteen of these electrodes were applied to record the low back muscle activity while the remaining were for reference signal collecting (three electrodes) and ground signal collecting (two electrodes). Then we collected the sEMG signal at a sample rate of 2,000 Hz and filtered it in a band of 15–950 Hz after amplifying it 2000 times (YRKJ-A2004, Zhuhai Yiruikeji Co., Ltd., China). The cardiac artifact and 50 Hz powerline influence was filtered by an independent component analysis (ICA) method (Hu et al., 2009; Mak, Hu, & Luk, 2010). In our previous study, it has been proved that the sEMG information during symmetrical flexion-extension trunk-movement was effective to evaluate the low back muscle’s performance and LBP rehabilitation (Hu et al., 2014; Hu et al., 2010). Therefore, in this study, we asked participants to do the flexion-extension trunk-movement and recorded the sEMG data during this period in a room with a constant temperature. Each subject performed the flexion-extension trunk-movement twice, with a 2–3 minutes rest period between attempts. The whole trunk-movement was done in the standing state under the supervision of physiotherapist and consisted of three time-phases (Fig. 2B). In the flexion phase, the participants bent the trunk forward up to degree from 20° to 30° measured by a protractor within about 1 second. In the sustention phase, they maintained this bending posture for about 2 seconds. In the extension phase, they extended the trunk and returned to the original standing posture within about 2 seconds.

Fig. 2

The detail about the sEMG topography. (A) Placement of the 3X7 electrodes on low back muscles. (B) Procedure of flexion-extension movement. (C) Standard sEMG topography and definition of the quantitative feature parameters extracted from topography. G means ground electrode, R means reference electrode, 1–16 means sEMG electrode from channel 1 to channel 16, RA means relative area, RW means relative width, RH means relative height.

After obtaining the original sEMG signal, we extracted the root mean square (RMS) from the signal with the 400 ms of calculating window. sEMG topography was constructed after we applied the method of linear cubic spline interpolation to fill the RMS space among the electrodes (Hu et al., 2014; Hu et al., 2010; Jiang et al., 2017). The dynamic time-varying sEMG topography of one healthy subject is shown in the Fig. 2C. The sEMG topography was the average from the recording of the twice flexion-extension trunk-movement. Then the RMS feature parameters named relative area (RA), relative width (RW) and relative height (RH) were extracted from the sEMG topography (Hu et al., 2014; Hu et al., 2010; Jiang et al., 2017). The method to calculate these RMS parameters was also shown in the Fig. 2C. In this study, the RMS value region above 60% was measured to calculate the RMS parameters.

According to our previous study, the root-mean-square difference (RMSD) feature parameter within flexion and extension phase, which represented the difference of the RMS parameter between the LBP patient and the healthy subject, were often applied for assessment of low back muscle activity’s change after rehabilitation (Hu et al., 2014; Jiang et al., 2017). Thus, in this study, we used RMSD of RA (RMSD RA), RMSD of RW (RMSD RW) and RMSD of RH (RMSD RH) within flexion and extension phase to investigate the change of low back muscle activity after tDCS program in patient with CLBP.

2.5 Adverse events

Study participants were asked to report any adverse events as well as other signs and symptoms at immediately post-intervention, and again at 24 hours after each of the intervention sessions. Participants were also closely observed by the assessor during the study session. The side effects of this tDCS system were expected to be itching, tingling, burning sensation, pain or warmth while the participant was using it.

2.6 Statistical analysis

SPSS 19.0 (IBM, Armonk, NY, USA) was applied to conduct all statistical analyses. The sample size calculation used in this study was based on previous research using tDCS for pain control (Fregni, Boggio, et al., 2006; Fregni, Gimenes, et al., 2006). A power analysis for an independent-sample t-test was conducted assuming one-tailed testing, an effect size of d = 1.32, 80% power and alpha error probability of α= 0.05. This analysis suggested a total sample size of at least 8 participants for each group. To take into account drop-out situation, exclusion situation and interindividual variability, we increased the sample size to 30 patients per group, thus including 60 patients. The demographic variables and clinical characteristics variables were compared with χ² test and independent T test. Since the distribution of the NRS data and the RMSD data was normal according to the Shapiro-Wilk test, to assess the effect of tDCS on NRS and RMSD, we used a two-way repeated measured analysis of variance (ANOVA) with the intervention (tDCS vs. sham) and time (pre-intervention vs. post-intervention) as factors. Partial eta squared $(η_{p}^{2})$ was calculated as a measure of the effect size. Mean square error (MSe) was also presented. If there is significant interaction effect for the variable, in order to interpret this significant interaction, we performed paired T test analysis of the time factor for each intervention condition separately. Two-tailed p values were set at 0.05.

2.7 Simulation of electric fields generated by tDCS on human brain

SimNIBS is an open-source simulation tool which could predict the local current generated by different size and position of tDCS electrodes (Saturnino et al., 2015). It was designed based on the finite element (FE) method. In order to analyze the distribution of current density of our new tDCS system on human brain, we used a sample brain model from SimNIBS 2.1.2 package in this study. The center of the anode electrode was placed over the C3 and the cathode electrode was over the contralateral supraorbital area. Then the cortical current density (ampere per meter squared, A/m²) was calculated for the 2 mA of stimulation. The anode circular electrode was 1 cm of diameter and 3.0 mm thickness and the cathode circular electrode was 4 cm of diameter and 3.0 mm thickness in the SimNIBS.

3 Results

3.1 Participants

A flow chart of the study is shown in Fig. 3. In this study, we recruited totally 60 patients with CLBP from March 2017 to March 2018. 9 patients were excluded because they declined to participant or did not meet the inclusion criteria. The remaining 51 patients (28 patients had lateralized pain and 21 patients had bilateral pain) were randomly assigned to the tDCS or sham group. Eventually, 26 patients received the real tDCS while the other 25 patients received the sham tDCS. The demographic characteristics and clinical characteristics were shown in the Table 1. There was no statistically significant difference between the tDCS and sham group. The age distribution of this two groups was also displayed in the Table 2.

Fig. 3

Flow chart of patients recruited to the study.

Table 1

Demographic of patients with low back pain in tDCS and sham group

	tDCS group	Sham group	P value
	(n = 26)	(n = 25)
Male/Female(n)	14/12	13/12	0.895^*
Age(years)	39.9(14.2)	44.1(13.0)	0.290^#
Weight(kg)	61.3(10.8)	61.5(11.8)	0.939^#
Height(cm)	164.2(8.0)	164.7(7.3)	0.823^#
BMI(kg/m²)	22.6(3.1)	22.6(3.7)	0.982^#
Pain duration (Months)	25.6(48.9)	29.5(46.2)	0.775^#
Baseline pain NRS (0–10)	5.1(1.9)	4.6(1.6)	0.311^#
Baseline ODI (0–100)	29.1(14.0)	26.4(11.8)	0.468^#
Baseline RMDQ (0–24)	6.8(4.7)	7.4(4.5)	0.627^#

BMI indicates body mass index. ODI Oswestry Disability Index. RMDQ Roland-Morris Disability Questionnaire. ^*Means χ² test, ^#means independent T test. Data except Male/Female(n) expressed as mean (standard deviation).

Table 2

Age distribution of tDCS group and sham group

Range of Age	Number of subject	Number of subject
(years)	(tDCS group)	(sham group)
18–30	8	5
31–40	5	4
41–50	7	8
51–65	6	8

3.2 Primary outcome: Changes in NRS for pain

The NRS score decreased from 5.12±1.91 to 3.34±1.73 in the tDCS group while changed from 4.60±1.60 to 4.36±1.77 in the sham group (Fig. 5). About 10 minutes after the post-intervention NRS measurement, we tried to ask the patient whether the NRS score was different with that immediately after tDCS program. The feedback showed there was no difference for all patients. From the Fig. 6, it could be found 17 of 26 patients in the tDCS group showed pain relief after tDCS program while only 8 of 25 patients in the sham group showed pain relief. What’s more, most of the pain-relief patients (14 patients) in tDCS group showed minimal clinically important difference (decrease of NRS score ≥2) after tDCS program while only 1 patient in sham group showed that. The minimal clinically important difference (MCID) for CLBP was 2-3 points reduction shown from previous studies (Lauridsen, Hartvigsen, Manniche, Korsholm, & Grunnet-Nilsson, 2006; Olsen et al., 2018; Ostelo & de Vet, 2005).

By repeated measures ANOVA, the NRS score showed significant Time×Intervention interaction effect [F(1,24) = 12.166, P = 0.002, $η_{p}^{2}$ = 0.336, MSe = 1.193]. The significant main effect was showed for Time $[F (1, 24) = 22.268, p < 0.000, η_{p}^{2} = 0.481, MSe = 1.127]$ but not for Intervention $[F (1, 24) = 0.113, p = 0.740, η_{p}^{2} = 0.005, MSe = 5.817]$ . By paired T test, the NRS showed significant difference between pre-intervention and post-intervention (P < 0.000) in the tDCS group as well as the sham group (P = 0.670).

3.3 Secondary outcomes

Table 3 showed the analysis results of repeated measures ANOVA for the RMSD values in sEMG topography. No statistically significant Time×Intervention interaction effect were found. Besides, the main effect for Time and Intervention did not showed any significance, except the RMSD RA at extension (Time).

Table 3
Comparison of RMSD parameters between tDCS and sham group using repeated measures ANOVA

Time Intervention Time×Intervention

Degree of Freedom MSe $η_{p}^{2}$ P value Degree of Freedom MSe $η_{p}^{2}$ P value Degree of Freedom MSe $η_{p}^{2}$ P value

RMSD RA at Flexion F(1,24) = 0.010 0.004 0.000 0.923 F(1,24) = 3.775 0.025 0.136 0.064 F(1,24) = 0.210 0.003 0.009 0.651

RMSD RW at Flexion F(1,24) = 0.001 0.006 0.000 0.977 F(1,24) = 2.597 0.021 0.098 0.120 F(1,24) = 0.499 0.004 0.020 0.487

RMSD RH at Flexion F(1,24) = 0.004 0.013 0.000 0.948 F(1,24) = 0.440 0.035 0.018 0.514 F(1,24) = 0.034 0.013 0.001 0.856

RMSD RA at Extension F(1,24) = 4.662 0.001 0.163 0.041* F(1,24) = 0.171 0.009 0.007 0.683 F(1,24) = 0.227 0.001 0.009 0.638

RMSD RW at Extension F(1,24) = 0.895 0.002 0.036 0.354 F(1,24) = 0.038 0.008 0.002 0.846 F(1,24) = 0.503 0.003 0.021 0.485

RMSD RH at Extension F(1,24) = 0.021 0.003 0.001 0.885 F(1,24) = 0.250 0.008 0.010 0.622 F(1,24) = 0.820 0.002 0.033 0.374

Time	Intervention	Time×Intervention
RMSD RA at Flexion	F(1,24) = 0.010	0.004	0.000	0.923	F(1,24) = 3.775	0.025	0.136	0.064	F(1,24) = 0.210	0.003	0.009	0.651
RMSD RW at Flexion	F(1,24) = 0.001	0.006	0.000	0.977	F(1,24) = 2.597	0.021	0.098	0.120	F(1,24) = 0.499	0.004	0.020	0.487
RMSD RH at Flexion	F(1,24) = 0.004	0.013	0.000	0.948	F(1,24) = 0.440	0.035	0.018	0.514	F(1,24) = 0.034	0.013	0.001	0.856
RMSD RA at Extension	F(1,24) = 4.662	0.001	0.163	0.041*	F(1,24) = 0.171	0.009	0.007	0.683	F(1,24) = 0.227	0.001	0.009	0.638
RMSD RW at Extension	F(1,24) = 0.895	0.002	0.036	0.354	F(1,24) = 0.038	0.008	0.002	0.846	F(1,24) = 0.503	0.003	0.021	0.485
RMSD RH at Extension	F(1,24) = 0.021	0.003	0.001	0.885	F(1,24) = 0.250	0.008	0.010	0.622	F(1,24) = 0.820	0.002	0.033	0.374

MSe indicates mean square error; $η_{p}^{2}$ indicates partial eta squared. RMSD indicates root-mean-square difference. RA relative area. RW relative width. RH relative height. ^*Means P < 0.05.

3.4 Adverse events

With respect to adverse effects, only one patient in tDCS group reported a severe dizziness during stimulation, but no one withdrew the experiment. The mild discomfort (itching and/or tingling), which typically faded out over a few minutes, was the most often reported side effect of both real and sham tDCS. No unexpected adverse events (e.g., seizure, headache, nausea) were observed during and after intervention.

3.5 Simulation results

The simulation results (Fig. 4) showed most of current was focus on the M1 while the peak value of current density was 0.225 A/m². The current flowed into the cortex and diverged from the center to the periphery. Although the current intensity was drastically decreased from the center of the stimulation site to the periphery, some regions of brain such as dorsolateral prefrontal cortex (DLPFC) and primary somatosensory cortex (S1) might still be influenced more or less, as the current density in part of these regions was still more than 0.112 A/m².

Fig. 4

Simulation results of current flow (current density and electric field) on human cortex. The color bar showed a scale for the current density with unit of A/m² and the electric filed with unit of V/m.

Fig. 5

Comparison of NRS value before and after stimulation in tDCS and sham groups. ^**Means P < 0.01 by paired T test.

Fig. 6

Change of pain intensity (NRS score) for all patients. NRS means Numeric Rating Scale.

4 Discussion

In this study, immediately after applying a single 20-minute session of 2mA tDCS program on M1 with a new dry stimulation electrode, it was found the pain intensity (NRS score) significantly decreased in CLBP patients (tDCS group) compared with the patients in the sham group. Nevertheless, the change of low back muscle activity (RMSD parameters from sEMG topography) showed no significant difference between the tDCS and sham groups.

The primary outcomes showed the pain intensity significantly decreased after a single session of tDCS program. The mechanism of pain modulation shown in previous findings can be used to account for this result. Pain is an unpleasant sensation whose range was from mild, localized discomfort to agony (Treede, 2006). It generally comprises a sensory component and a reaction/processing component (Bushnell, Ceko, & Low, 2013; Fernandez & Turk, 1992; Millan, 1999; Price, 2000). The sensory component is a bottom-up component because the pain information passes from the peripheral receptors (nociceptors) stimulated by some external (e.g. pressure, temperature) or internal impairment (e.g. burning, aches) to the pain center in the brain along the afferent pathways (Millan, 1999). The reaction/processing component is a top-down component because pain sensation can often be modified by the affective (e.g. anger, fear, sadness) and cognitive factors (e.g. anticipation, attention, hypnosis, placebos) (Bushnell et al., 2013; Price, 2000). According to the pain model, it has been found that tDCS may affect both bottom-up and top-down dimension of pain model (Fregni, Boggio, et al., 2006; García-Larrea et al., 1999; Garcia-Larrea et al., 1997; Nitsche & Paulus, 2000; Polanía et al., 2012). Some studies showed that the motor-cortical excitability significantly increased during anodal tDCS and significantly decreased during cathodal tDCS by recording the transcranial magnetic stimulation (TMS)-evoked motor evoked potentials (MEPs) (Nitsche & Paulus, 2000). The activation of motor-cortical excitability could alter the cortico-striato-thalamic circuit (Polanía et al., 2012) and then modulate the thalamic to inhibit the pain impulses from spinal cord (Fregni, Boggio, et al., 2006). The thalamic nuclei activation may also lead to several events in other pain-related structures (e.g. anterior cingula, periaqueductal gray) which could modulate the affective-emotional factors of pain (García-Larrea et al., 1999; Garcia-Larrea et al., 1997). Therefore, the possible reason accounting for the decrease of pain intensity after tDCS in this study could be that the modulation of the bottom-up dimension, or top-down dimension, or both, of the LBP pathway. Besides, for the reason why single session of tDCS could reduce pain, the findings from previous studies may give an answer. They found a session with 10–40 minutes and 1–4 mA could significantly change the brain activity immediately and the effect could last for a long time without irreversible injury (Bikson et al., 2016; Reinhart, Cosman, Fukuda, & Woodman, 2017; Thair, Holloway, Newport, & Smith, 2017). Thus, in this study, only one session with 20 minutes and 2 mA could affect the brain activity and processing procedure for pain.

In this study, it could be found that the dynamic sEMG topography (secondary outcome) in CLBP patients did not significantly change after single-session tDCS. This finding was consistent with another previous study. It showed the average cortical maps of paraspinal muscle responses to TMS and the range of motion of forward flexion assessed by Schober test in LBP group did not significantly change while the pain intensity decreased after seven consecutive days’ tDCS intervention (Schabrun et al., 2014). The possible interpretation of these findings might refer to some previous studies. Some researchers found the block of bottom-up pain pathway could lead to the alteration of muscle activity by inhibiting the release of the neurotransmitter and acetylcholine at the neuromuscular junction (Amann, Proctor, Sebranek, Pegelow, & Dempsey, 2009; Aoki, 2003). It meant the inhibition of pain pathway to brain could change the control to the muscle. With respect to the top-down dimension of pain, the study results showed that different psychological factors might have different effects on the muscle activity (Beach, Coke, & Callaghan, 2006; Burns, 2006; Burns, Bruehl, & Quartana, 2006; Ruscheweyh, Kreusch, Albers, Sommer, & Marziniak, 2011). By emotion-induced interview, it could be found that anger could change the muscle tension near the site of injury in patients with CLBP while sadness could not (Burns, 2006; Burns et al., 2006). By cognitive task, it could be found that the distraction of pain could only decrease the pain intensity without alteration of muscle activation while the concentration-on-pain task could increase the pain intensity and affect the muscle activation (Beach et al., 2006; Ruscheweyh et al., 2011). Therefore, if the intervention to top-down dimension of pain decreased the pain intensity, the muscle activity often would not alter. It might be the reason why the sEMG topography in CLBP patients showed no significant change after tDCS program. Then not only the single session of tDCS, but also several consecutive days’ tDCS program might mainly affect the top-down dimension of LBP model.

The simulation results in this study showed that the peak of current density on M1 was 0.225 A/m². According to previous studies (Bikson et al., 2016), the injury threshold levels of current density found in animals was 6.3–17 A/m² and the maximum predicted brain current density was 0.23 A/m² for a small adult head and 0.32 A/m² for pediatric head. For different simulation parameters (spanning head size, tDCS dose and model parameterization) in literature, the peak current densities ranged from 0.0828 to 0.211 A/m² (Laakso & Hirata, 2013; Mekonnen, Salvador, Ruffini, & Miranda, 2012; Rampersad et al., 2014). Thus, theoretically, the current density from our study would not bring any risk for brain injury to the human subjects. This conclusion was also supported by our experiment results which showed no serious adverse effects were found during and after tDCS intervention.

Although a lot of studies including this study showed the M1-tDCS could relieve CLBP, there still existed some negative or null findings in previous studies. O’Connell, et al. (O’Connell et al., 2013) recruited 8 participants and asked them to enter a 15-day tDCS experimental period. They found no significant effect in the primary outcomes between active and sham stimulation (average pain intensity p = 0.821, unpleasantness p = 0.937) or across any other clinical variables. Luedtke et al. (Luedtke et al., 2015) recruited participants to receive real or sham tDCS for five consecutive days immediately before cognitive behavioral management. Analyses of covariance with baseline values (pain or disability) as covariates showed that tDCS was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval – 8.69 mm to 6.3 mm; P = 0.68)) and disability (difference between groups 1 point (– 1.73 to 1.98; P = 0.86)). In these negative studies, the researchers often used the saline-soaked surface sponge electrodes. It could lead to the low current intensities reaching cortex. By improving the stimulation electrodes and/or increasing the stimulation duration, more electrical current can be delivered to the cortex effectively. It was one of the important reasons why we conducted this study.

There are several limitations to this study. Firstly, we only investigated the effect of single-session tDCS rather than several consecutive days’ tDCS, because previous study has shown the effect of several consecutive days’ tDCS using large 35 cm² (5×7 cm) saline-soaked surface sponge tDCS electrodes. In order to further investigate the effect of our tDCS system using dry electrode, it is meaningful to recruit CLBP inpatients and apply several consecutive days’ tDCS in the future. Secondly, the psychological scale such as Beck Depression Inventory-II (BDI-II) (Poole, Bramwell, & Murphy, 2006) was not measured for CLBP patients because it was difficult to assess it in the single-session tDCS program and most of outpatients declined to attend or finish this assessment due to the long assessment and treatment duration. Therefore, this scale will be assessed in the future when inpatients are recruited and the several consecutive days’ tDCS program is applied. In addition, because it was still difficult to assure whether the adjacent cortices near M1 (e.g. DLPFC, S1) were stimulated or not, the excitability of M1, DLPFC and S1 needed to be measured to make the mechanistic explanation more convincible. We will measure the electroencephalography (EEG) or TMS-EEG or MEPs in the future. Last but not least, only 2 mA of current was used to stimulate the target cortex because previous studies using saline sponge electrodes showed this current intensity was effective and safe for pain relief. Future studies should test the optimal stimulation current intensity for the novel dry electrode tDCS system using scanned individual brain model.

5 Conclusions

In summary, in this study, by using a single 20-minute session of tDCS on M1 site via dry electrode based on 10–20 EEG electrode placement system, CLBP patients showed immediate decrease of pain intensity (NRS score) but no significant alteration of low back muscle activity (sEMG topography). The results demonstrated the usefulness of tDCS on M1 site with a rapid and effective relief of CLBP, and indicated the mechanism of pain modulation might be affecting the top-down modulation pathway of pain.

Conflicts of interest

The authors declare no conflict of interest.

Footnotes

Acknowledgments

This work was supported by National Natural Science Foundation of China (81572193), Hong Kong RGC GRF (17656116) and China Postdoctoral Science Foundation (2018M643264).

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