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ORIGINAL ARTICLE

Randomized clinical trial comparing of

transcranial direct current stimulation
(tDCS) and transcutaneous electrical nerve
stimulation (TENS) in knee osteoarthritis
Simin Sajadi, Malihe Karimi, Bijan Forogh, Gholam Reza Raissi,
Forugh Zarnegar , Tannaz Ahadi ∗

Neuromusculoskeletal Research Center, Iran University of Medical Sciences, Tehran, Iran

Received 17 May 2020; accepted 20 August 2020

KEYWORDS Abstract
Exercise; Background. — Due to the limitations of pharmacological and surgical management of knee
Knee osteoarthritis; osteoarthritis (OA), several non-pharmacologic approaches including transcutaneous electri-
Transcranial direct cal nerve stimulation (TENS) and transcranial direct current stimulation (tDCS) have been
current stimulation; introduced, with promising results.
Transcutaneous Objective. — We aimed to investigate and compare the therapeutic effects of TENS and tDCS
electrical nerve for the treatment of patients with knee OA.
stimulation; Methods. — In this double-blinded randomized controlled trial, a total of 40 adult patients with
VAS; knee OA were randomly allocated to either the TENS or the tDCS group. Patients in either
WOMAC group received 6 sessions of the TENS or tDCS for 2 weeks. Knee strengthening exercises were
performed twice daily for the entire treatment period. Patients were evaluated using the visual
analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC).
Results. — Significant improvement was observed in all outcomes in both TENS and tDCS groups
at each follow up compared to baseline although the early improvement (first follow-up) in the
WOMAC index was not significant in the TENS group. Based on the within-subject analysis, the
behavior of two treatment groups did not differ regarding the changes in the course of the VAS,
WOMAC score and its subscales, i.e. stiffness, pain and function (p = 0.263, 0.051, 0.198, 0.075,
and 0.146, respectively).

∗ Corresponding author at: Neuromusculoskeletal Research Centre, Firoozgar Hospital, Valiasr Square, Behafarin Avenue, Tehran, Islamic

Republic of Iran.
E-mail address: Ahadi.t@iums.ac.ir (T. Ahadi).

https://doi.org/10.1016/j.neucli.2020.08.005
0987-7053/© 2020 Published by Elsevier Masson SAS.

Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
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NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
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Conclusions. — Based on the results of this study, the effect of tDCS and TENS was not signifi-
cantly different on pain and function of patients with knee OA.
© 2020 Published by Elsevier Masson SAS.

Introduction medial thalamus, anterior cingulate and upper brainstem

[19,33].
Osteoarthritis (OA) is the most common chronic rheumatic It has been shown that knee OA and its pain could
disease and the leading cause of pain, impairment, and dis- be associated with gray matter atrophy, reorganization in
ability in the aging population [41]. OA is characterized by somatosensory and motor cortex and neuroplasticity state
joint pain, stiffness, swelling, and limitation of joint func- adjustment. These could be altered through tDCS central
tion due to structural and functional failure of the synovial effects [14]. Several recent studies have investigated the
joints [13]. The most commonly affected joints are the tDCS role in the management of knee OA with promising
knees, representing about 83 % of the total OA burden on the results [4].
health system [37]. Knee OA is a progressive and debilitat- Thus, beneficial effects of TENS through peripheral stim-
ing condition with an estimated radiologic and symptomatic ulation and tDCS through cortical stimulation have been
prevalence of 37 % and 12 %, respectively, in individuals aged shown in the management of knee OA but to the best of our
60 years or older [20,25,45]. knowledge, no previous research has compared these two
Pain caused by knee OA is associated with progression treatment modalities. We conducted this study to investi-
of the degenerative process and is the main reason causing gate and compare the therapeutic effects of tDCS and TENS
patients to seek medical advice [40]. Current knee OA treat- for the treatment of patients with knee OA.
ment strategies mainly focus on reducing pain and improving
patients’ function and participation [27]. In advanced Methods
OA, surgical interventions such as total knee replacement
are the treatment of choice [43]. Several non-operative
Study design and setting
approaches have been described in the early stage of this
disease, including non-steroidal anti-inflammatory drugs
This randomized controlled trial study was a double-center
(NSAID), weight loss, exercise, modification of activities of
study, conducted at the Physical Medicine and Rehabilita-
daily living, orthoses, physical therapy and intra-articular
tion clinic of the Shafa Yahyaian Hospital and Firoozgar
injections [43].
Hospital in 2019−2020. The study was approved by the
The management of knee OA is challenging, especially
ethics committee of the Iran University of Medical Sciences
in elderly patients. Pharmacological therapy often provides
(IUMS). Research was carried out according to the Helsinki
only limited pain relief and carries the risk of adverse
Declaration and informed written consent was obtained
effects [1]. Furthermore, surgical interventions may not be
from all participants. The study was registered in the Ira-
feasible in older patients due to comorbidities [26]. There-
nian Registry of Clinical Trials (#IRCT20190804044431N1;
fore, other conservative non-pharmacologic approaches
https://www.irct.ir/trial/42,035).
have been evaluated [26].
Transcutaneous electrical nerve stimulation (TENS) is a
physical modality that involves electric current delivered Participants
via superficial electrodes placed on the skin [47]. It is a cost-
effective, feasible neuromodulation therapy first introduced Of 57 evaluated patients, 40 patients (34 females) aged
in 1965 and widely used in many pain management strate- 51—71 years were enrolled in this study. The inclusion cri-
gies including knee pain [37]. The analgesic effect of TENS teria were patients aged > 50 years with knee OA diagnosis
is considered to be based on the’ Gate-Control Theory’ of based on the American College of Rheumatology (ACR) cri-
pain perception or stimulation of ␤ endorphin production teria [5]: moderate knee OA (grades II and II based on the
[34]. Several systematic reviews demonstrated that TENS Kellgren-Lawrence radiologic criteria [23]), pain intensity
has effective pain relief on knee OA [38]. of ≥ 40 on visual analogue scale (VAS) while weight bear-
In recent years, several authors investigated the effect ing and knee pain for at least 6 months. Patients with any
of interventions targeting the central nervous system (CNS) neurologic and musculoskeletal disorders affecting lower
in ameliorating pain. Transcranial direct current stimula- extremity function, knee joint inflammatory disorders, sec-
tion (tDCS) is a noninvasive technique to modulate cortical ondary OA, development of other knee pathology during the
excitability [18]. During tDCS, a weak direct electric current study, radicular back pain, diabetes mellitus (DM), major
is applied to the brain via several electrodes [1]. Electrical depressive disorder (MDD), history of knee surgery, history of
stimulation of primary motor cortex (M1) can modulate pain drug abuse, epilepsy, acute or chronic infection, pregnancy,
through activation of thalamic nuclei directly connected unstable conditions, electrical implants such pacemakers,
with motor and premotor cortices, as well as activation of or metal implants near electrode locations were excluded.

Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
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NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
tDCS vs TENS in knee OA 3

Of 57 assessed participants, 17 subjects were not Pain intensity was measured using a 100 cm VAS (0 = no
enrolled in the study (10 due to unwillingness to partici- pain at all and 100 = the worst pain possible), a reliable
pate in this study, 3 with VAS < 40, 2 with a history of knee index for pain evaluation [7]. Patients were asked to mark
surgery, and 2 with a history of epilepsy). the maximum pain they had experienced in the last two days
History and demographic information were obtained from on the VAS ruler.
all patients before the intervention. The WOMAC Index is one of the most widely used ques-
tioners for evaluating OA patients. It is composed of 24
questions organized into 3 subscales, measuring stiffness,
Randomization, patient enrolment and blinding pain, and physical function. Answers to each of the 24
questions are scored on 5-point Likert scales (none = 0,
40 subjects were randomly assigned to one of 2 treatment slight = 1, moderate = 2, severe = 3, extreme = 4), with total
groups, the TENS group (n = 20) or the tDCS group (n = scores ranging from 0 to 96. Higher scores indicate greater
20), using randomly generated treatment allocations within disease severity. The validity and reliability of the Persian
sealed envelopes. The physician who evaluated the outcome version of WOMAC have been described by Nadrian et al. in
measures, the participants, and the person responsible for 2012 [30].
data analysis were all blinded to the group allocation. Any adverse effect of interventions was registered.

Intervention Sample size

Patients in each group received 6 sessions of intervention Sample size was calculated using the study by Chang et al.
over a 2-week period (3 sessions per week). [10]. According to this study and an alpha of 0.05, a test
In the TENS group, patients were positioned in the supine power of 80 %, confidence interval of 95 % and considering a
position and the electrical current was applied to the most 20 % dropout, a minimum of 20 patients for each group was
painful part of the affected knee. We positioned 4 rubber calculated.
electrodes with a surface of 35 cm2 in a square pattern
around the kneecap, approximately 5 cm apart, centered Statistical analysis
over the pain point. The treatment current was applied using
conventional TENS with the following parameters: frequency Outcome measures were analyzed using SPSS software V24.
of 100 Hz; pulse width of 100 ␮s; and intensity of 10 % below The Kolmogorov—Smirnov test revealed normal distribution
the patient motor threshold for 25 min. of data, so parametric tests were used. Independent sam-
In the tDCS group, using a battery driven stimulator (Acti- ple t-test and Chi-square test were used for analysis of
vadose II), a constant current with an intensity of 2 mA was baseline characteristics. The interaction effect of time and
applied for 20 min per session through 2 rubber electrodes group on outcome measures were evaluated using mixed
with a surface of 35 cm2 and covered with 0.9 % saline soaked ANOVA and post hoc tests (confidence interval (CI) = 95 %).
sponges. The anode electrode was placed over the M1 (C3 or A Greenhouse-Geisser correction was used in the event of
C4 according to the 10—20 system of electroencephalogra- sphericity violation. Statistical significance was considered
phy electrode placement) on the hemisphere contralateral to be less than 0.05.
to the affected knee, and the cathode electrode was placed
over the ipsilateral supraorbital (SO) area (M1-SO montage).
This positioning was based on the previous studies that found Results
this montage effective for pain alleviation in knee OA [1].
In both groups, strengthening exercises of the knee mus- During the course of the study, none of the participants
cle were taught to all participants by a physical medicine dropped out and all 40 subjects attended treatment and
and rehabilitation specialist. These consisted of closed chain follow-up sessions. Finally, 20 patients in both the TENS and
strengthening exercise of the quadriceps muscle (e.g. wall tDCS groups were analyzed. No significant differences were
squat, Forward Step-up, lunges) and patients were told to do observed between two treatment groups regarding demo-
the mentioned exercises twice a day during the treatment graphic and patients’ baseline characteristics (Table 1).The
period. interaction effect of time and group was not significantly
Patients were advised to withhold all analgesic at different when evaluating VAS (df = 2.33, F = 1.35, p = 0.263)
least 1 week before entering the study and to only use (Fig. 1), WOMAC score (Fig. 2) and its subscales, i.e. stiff-
acetaminophen in case of pain intensity > 60 on VAS. ness, pain and function (df = 3, F = 2.66, p = 0.051;df = 3,
F = 1.58, p = 0.198; df = 2.22, F = 2.58, p = 0.075; df = 2.58,
F = 1.87, p = 0.146, respectively).This implies that the behav-
Outcome measures ior of two treatment groups did not differ regarding the
changes in the course of the above-mentioned outcomes
Patients’ symptoms and function were assessed by the Visual (Table 2).
Analogue Scale (VAS) and Persian version of the Western In the tDCS group, significant improvement was observed
Ontario and McMaster Universities Osteoarthritis (WOMAC) regarding all outcomes when comparing the baseline val-
index. All outcome measures were assessed at baseline, 1 ues to follow-up evaluations (i.e. baseline to 1st follow-up,
week, 1 month and 3 months after the end of the last treat- baseline to 2nd follow-up and baseline to last follow-up). In
ment session. the TENS group, the same result was observed only in the VAS

Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
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NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
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Table 1 Participant demographics and baseline evaluations.

Characteristic TENS tDCS P- value

Number 20 20
Sex, n (%)
Male 1 (5) 5 (25) 0.091
Female 19 (95) 15 (75)
Age (year), mean (Std. deviation) 56.85 (5.81) 59.30 (6.13) 0.202
BMI (kg/m2 ), mean (Std. deviation) 31.76 (5.04) 30.29 (4.68) 0.347
VAS, mean (Std. deviation) 71.00 (15.18) 68.50 (19.54) 0.654
WOMAC total, mean (Std. deviation) 51.50 (16.13) 53.40 (18.03) 0.727
WOMAC stiffness, mean (Std. deviation) 4.15 (1.31) 4.35 (1.98) 0.708
WOMAC pain, mean (Std. deviation) 10.55 (3.49) 11.40 (3.46) 0.443
WOMAC function, mean (Std. deviation) 36.80 (12.73) 37.65 (13.44) 0.838
TENS: Transcutaneous Electrical Nerve Stimulation; tDCS: Transcranial Direct Current Stimulation; BMI: Body Mass Index, VAS: Visual
Analogue Scale, WOMAC: The Western Ontario and McMaster Universities Osteoarthritis Index.

Table 2 The between-group analysis of outcome measures within treatment group.

Outcome Before intervention 1 week After 1 month After 3 months after P- value*

VAS, mean (Std. deviation)

TENS 71.00 (15.18) 55.00 (17.92) 43.50 (19.81) 45.00 (23.95) 0.263
tDCS 68.50 (19.54) 46.00 (20.11) 45.00 (27.63) 48.00 (25.07)
WOMAC total, mean (Std. deviation)
TENS 51.50 (16.13) 48.75 (19.79) 34.55 (20.38) 37.05 (22.92) 0.051
tDCS 53.40 (18.03) 40.70 (14.73) 31.65 (15.94) 26.35 (15.77)
WOMAC stiffness, mean (Std. deviation)
TENS 4.15 (1.31) 3.85 (1.93) 2.25 (1.97) 2.30 (2.06) 0.198
tDCS 4.35 (1.98) 3.25 (1.86) 2.70 (1.94) 1.90 (1.89)
WOMAC pain, mean (Std. deviation)
TENS 10.55 (3.49) 10.40 (4.77) 8.10 (4.95) 8.00 (6.58) 0.075
tDCS 11.40 (3.46) 8.65 (3.03) 6.85 (3.45) 5.45 (3.50)
WOMAC function, mean (Std. deviation)
TENS 36.80 (12.73) 34.50 (14.46) 24.20 (14.54) 25.40 (16.63) 0.146
tDCS 37.65 (13.44) 29.10 (10.47) 21.95 (11.30) 18.55 (11.41)
* The P-value for Group and Time interaction.
TENS: Transcutaneous Electrical Nerve Stimulation; tDCS: Transcranial Direct Current Stimulation; VAS: Visual Analogue Scale; WOMAC:
The Western Ontario and McMaster Universities Osteoarthritis Index.

measures. The early improvement in the WOMAC score and toward 1 month after the end of treatment and their improv-
its subscales was not significant at the 1st follow-up, though ing effect was preserved for another 2 months. Furthermore,
they improved significantly at second and third follow-up vs. the early improvement (within the first week after thera-
baseline. At the 3-month evaluation, a slight non-significant peutic course) in patients’ pain and function (based on the
increase was observed in the VAS (second vs third follow- WOMAC index) was significant only in patients who received
up) in both treatment groups and in WOMAC total score and tDCS.
subscales of stiffness and function in TENS group, though all Anodal tDCS has been associated with pain reduction
these measures were significantly lower than baseline values in various chronic pain syndromes including fibromyalgia
(Table 3). [16], multiple sclerosis [29] and chronic recurrent low back
There was no adverse effect in either group. pain (CRLBP) [36]. Several recent studies have demon-
strated potential effects of tDCS with M1-SO montage in
Discussion patients with knee OA. In Chang et al.’s study [10] tDCS
plus exercise was significantly associated with increased
pain threshold compared to sham tDCS plus exercise. Both
This study was conducted to evaluate the efficacy of tDCS
techniques were associated with significant pain reduc-
and TENS combined with home knee strengthening exercises
tion in the first week after an 8-week period of treatment
in patients with knee OA. According to the findings of the
sessions (2 sessions/week) although pain during walking
present study, both TENS and tDCS combined with exercise
decreased two-fold in tDCS compared to sham tDCS (41.4
improved patients’ knee pain (evaluated by VAS and WOMAC
vs 20.7in VAS). Function measured by WOMAC improved
score) and functional condition (evaluated by WOMAC score)

Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
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tDCS vs TENS in knee OA 5

Table 3 The analysis of outcome measures in treatment groups.

Outcome Baseline vs 1st Baseline vs Baseline vs 1st vs2nd 2nd vs3rd

follow-up 2nd follow-up 3rd follow-up follow-up follow-up

VAS, mean Difference (95% CI)

TENS 16.00 (4.2—27.7 )B 27.50 (14.0—40.9)B 26.00 (9.3—42.6)C 11.50 (2.7—20.2)B −1.50 (-13.6—10.6)A
tDCS 22.50 (10.7—34.2) C
23.50 (10.0—36.9)C 20.50 (3.8—37.1)B 1.00 (-7.7—9.7)A −3.00 (-15.1—9.1)A
WOMAC total, mean Difference (95% CI)
TENS 2.75 (-7.3—12.8)A 16.95 (7.9—25.9)C 14.45 (3.9—24.9)B 14.20 (5.0—23.3)B −2.50 (-9.6 to 4.6)A
B
tDCS 12.70 (2.5—22.8) 21.75 (12.7—30.7)C 27.05 (16.5—37.5)C 9.05 (-0.1—18.2)A 5.30 (-1.8—12.4)A
WOMAC stiffness, mean Difference (95% CI)
TENS 0.30 (-0.7 to 1.3)A 1.90 (0.7—3.0)C 1.85 (0.5—3.1)B 1.60 (0.7—2.4)C −0.05 (-1.0 to 0.9)A
tDCS 1.10 (0.0—2.1)B 1.65 (0.5—2.7)B 2.45 (1.1—3.7)C 0.55 (-0.3 to 1.4)A 0.80 (-0.1—1.7)A
WOMAC pain, mean Difference (95% CI)
TENS 0.15 (-1.9 to 2.2)A 2.45 (0.2—4.6)B 2.55 (-0.3—5.4)A 2.30 (-0.2—4.8)A 0.10 (-1.8 to 2.0)A
tDCS 2.75 (0.6—4.8)B 4.55 (2.3—6.7)C 5.95 (3.0—8.8)C 1.80 (-0.7 to 4.3)A 1.40 (-0.5 to 3.3)A
WOMAC function, mean Difference (95% CI)
TENS 2.30 (-0.5—10)A 12.60 (6.0—19.0)C 11.40 (4.0—18.0)B 10.30 (3.4—17.1)B −1.20 (-5.9 to 3.5)A
B
tDCS 8.55 (0.5—16.0) 15.70 (9.1—22.3)C 19.10 (11.7—26.4)C 7.15 (0.2—14.0)B 3.40 (-1.3—8.1)A
A: No statistical significance. (P-Value > 0.05).
B: statistical significance. (P-Value ≤ 0.05).
C: statistical highly significance. (P-Value < 0.001).
1stfollow-up: 1 week after the end of intervention; 2ndfollow-up: 1 month after the end of intervention; 3rdfollow-up: 3 months after
the end of intervention.
CI: Confidence Interval; TENS: Transcutaneous Electrical Nerve Stimulation; tDCS: Transcranial Direct Current Stimulation; VAS: Visual
Analogue Scale; WOMAC: The Western Ontario and McMaster Universities Osteoarthritis Index.

Fig. 1 VAS changes in two treatment groups during the study Fig. 2 WOMAC changes in two treatment groups during the
period. study period.

only in the tDCS plus exercise group. The between-group of 2 mA intensity for 20 min can reduce experimental pain
analysis showed no significant difference regarding their sensitivity and facilitate pain inhibition. These changes in
outcome measures. Ahn et al. [2] performed tDCS with a experimental pain measures were associated with pain alle-
shorter treatment interval (5 daily sessions). They reported viation. Another study by Ahn et al. [1] showed that daily
better pain improvement in the tDCS group compared to tDCS for 5 sessions was associated with improved mobility in
the sham group (p = 0.03). Interestingly, the pain improve- elderly patients with knee OA (a mean difference of 15.74 m
ment effect started after the first treatment session and compared to sham, p = 0.105).
it was preserved through 3-week follow-up evaluations. Historically, pain in knee OA was considered to be a
Of note, though marginally better functional improvement regional pain condition caused only by regional peripheral
and mobility performance were observed with tDCS (eval- nociceptive afferents [32]. Recent studies confirmed that
uated by WOMAC index and 6-Minute Walk Test (6MWT), central pain sensitization has a vital role in knee OA, lead-
respectively), the difference was not statistically significant ing to local and widespread hyperalgesia in these patients
between the two treatment groups. [15,28]. tDCS with M1-SO montage could modulate the pain
According to another study by Ahn et al. in 2018 [3], 5 central pathways (M1-thalamic inhibitory connections) and
sessions of daily M1-SO tDCS with a constant direct current so, the central sensitization [17,42]. Thus, it could increase

Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
+Model
NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
6 S. Sajadi et al.

the brain’s excitability level and responsiveness to other more, tDCS is considered as an effective means of provoking
interventions such as knee exercises [31,35]. sustained changes in regional neural activity [24].
There is no consistent protocol for the management In the present study, significant analgesic effect and
of knee OA with tDCS. The ideal effects of tDCS could functional improvement were observed in patients received
depend on several factors including stimulation parame- TENS, in line with previous studies. Chen et al. [12]
ters, treatment duration and intervals, the polarity of the suggested that TENS is a better treatment compared to
electrode, the target brain area, electrode preparation intra-articular injection of hyaluronic acid in patients with
methods and the target population [46]. Of note, 2 mA inten- knee OA. According to their result, both treatments were
sity was associated with increased excitability under either associated with improved pain (evaluated by VAS) and
anode or cathode. In contrast, the 1 mA intensity resulted function (evaluated by the Lequesne index) toward the 3-
in increased excitability under the anode and decreased month follow-up. At the 2-week follow-up, better pain relief
excitability under the cathode [3]. So, the underlying pain and functional improvement were observed in the TENS
reduction mechanism could alter between studies using dif- group; at the last follow-up session, functional improvement
ferent current intensity as observed in Ahn’s studies [1—4] was significantly greater in the TENS group. Conversely, in
(2 mA tDCS) compared to Chang’s study [10] (1 mA tDCS). Vance et al.’s study [44], active TENS was associated with
Some authors have evaluated the efficiency of tDCS com- increased pressure pain threshold over the knee and tibialis
bined with peripheral electrical stimulation (PES). Boggio anterior muscle. However subjective pain at rest and during
et al. [9] evaluated the combination of tDCS and TENS movement significantly reduced in active as well as placebo
in patients with chronic neurogenic pain of the arm. In TENS.
their study, all patients underwent 3 different treatments: In the meta-analyses of 14 randomized controlled tri-
TENS + tDCS, sham TENS + tDCS, and Sham TENS + sham tDCS. als (RCT) by Chen et al. [11], a significant analgesic effect
The treatment order was randomly selected in each patient was observed with TENS compared to control groups (mean
and there was a 48 -h interval between each session. In this difference of -0.79; p < 0.01). Although a better WOMAC
study, only early assessment was performed, i.e., immedi- score was observed in TENS groups, the difference was slight
ately after the treatment session. According to their result, and not statistically significant. According to the Cochrane
significant pain alleviation was observed in two active groups review by Rutjes et al. [34], a mean difference of 0.07 was
(TENS + tDCS and tDCS + sham TENS). Furthermore, the two- observed in VAS between TENS and control groups in favor
fold pain reduction in the TENS + tDCS compared to other of the ES modality.
treatment groups, was statistically significant (p = 0.02). Many factors such as dosing, interaction with drugs, pop-
Hazime et al. [22] reported similar results with the com- ulation, outcome measures and timing of the assessment
bined tDCS and PES in patients with CRLBP. Better analgesic could influence TENS results which may explain different
effect was observed with the tDCS + PES in the short-term results of the previous studies [39].
follow-up and patients’ pain improved up to 3 months only in The present randomized clinical trial compared the
the tDCS + PES group. No group revealed significant improve- effect of tDCS with TENS on knee OA for the first time,
ment longer-term evaluation (6-months). Furthermore, da but the results should be interpreted in the light of several
Graca-Tarragó et al. [14] reported that tDCS combined with limitations. The main limitations were a limited follow-up
intramuscular electrical stimulation (EIMS) (5 daily sessions) period (3 months) and the lack of a sham group. Further
had significant additive analgesic effects with respect to study with longer follow-up duration, evaluation of differ-
either of the two modalities in patients with knee OA. ent tDCS protocols and comparison of TENS + tDCS with TENS
Several hypotheses have been put forward to explain this and tDCS and sham intervention is recommended for better
synergy. Schabrun et al. [36] suggested that the analgesic evaluation of these modalities.
effects of the two techniques could be combined for a bet-
ter outcome. Hazime et al. [22] described the metaplasticity Conclusion
phenomenon. Based on this hypothesis, the combination of
an inhibitory technique (high-frequency PES at the sensory
Based on the results of this study, there were no signifi-
level) with another excitatory intervention (anodal tDCS)
cant differences between tDCS and TENS groups on pain and
may increase the effectiveness of each technique via home-
function of patients with knee OA.
ostatic plasticity [6]. Bocci et al. [8] have also demonstrated
the effect of tDCS combined with rTMS on metaplasticity of
human visual cortex. Conflicts of interest
On the other hand, Harvey et al. [21] found no addi-
tional effect for combined tDCS with TENS over TENS alone No conflicts are declared.
in patients with pelvic pain.
Several side effects have been associated with tDCS in the
Acknowledgments
literature including fatigue during cranial stimulation and
reduced seizure threshold, headache, mood change, visual
changes, nausea and insomnia after the treatment session This study did not receive any financial support.
[2]. The studies evaluating M1-SO montage in patients with
knee OA reported no or limited side effects [2,10]. Similarly, References
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Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
+Model
NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
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Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005
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Please cite this article in press as: Sajadi S, et al. Randomized clinical trial comparing of transcranial direct cur-
rent stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis. Neurophysiologie
Clinique/Clinical Neurophysiology (2020), https://doi.org/10.1016/j.neucli.2020.08.005