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Neurophysiologie Clinique/Clinical Neurophysiology (2020) xxx, xxx—xxx

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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
+Model
NEUCLI-2718; No. of Pages 8 ARTICLE IN PRESS
2 S. Sajadi et al.
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
Osteoarthritis (OA) is the most common chronic rheumatic
disease and the leading cause of pain, impairment, and dis-
ability in the aging population [41]. OA is characterized by
joint pain, stiffness, swelling, and limitation of joint func-
tion due to structural and functional failure of the synovial
joints [13]. The most commonly affected joints are the
knees, representing about 83 % of the total OA burden on the
health system [37]. Knee OA is a progressive and debilitat-
ing condition with an estimated radiologic and symptomatic
prevalence of 37 % and 12 %, respectively, in individuals aged
60 years or older [20,25,45].
Pain caused by knee OA is associated with progression
of the degenerative process and is the main reason causing
patients to seek medical advice [40]. Current knee OA treat-
ment strategies mainly focus on reducing pain and improving
patients’ function and participation [27]. In advanced
OA, surgical interventions such as total knee replacement
are the treatment of choice [43]. Several non-operative
approaches have been described in the early stage of this
disease, including non-steroidal anti-inflammatory drugs
(NSAID), weight loss, exercise, modification of activities of
daily living, orthoses, physical therapy and intra-articular
injections [43].
The management of knee OA is challenging, especially
in elderly patients. Pharmacological therapy often provides
only limited pain relief and carries the risk of adverse
effects [1]. Furthermore, surgical interventions may not be
feasible in older patients due to comorbidities [26]. There-
fore, other conservative non-pharmacologic approaches
have been evaluated [26].
Transcutaneous electrical nerve stimulation (TENS) is a
physical modality that involves electric current delivered
via superficial electrodes placed on the skin [47]. It is a cost-
effective, feasible neuromodulation therapy first introduced
in 1965 and widely used in many pain management strate-
gies including knee pain [37]. The analgesic effect of TENS
is considered to be based on the’ Gate-Control Theory’ of
pain perception or stimulation of ␤ endorphin production
[34]. Several systematic reviews demonstrated that TENS
has effective pain relief on knee OA [38].
In recent years, several authors investigated the effect
of interventions targeting the central nervous system (CNS)
in ameliorating pain. Transcranial direct current stimula-
tion (tDCS) is a noninvasive technique to modulate cortical
excitability [18]. During tDCS, a weak direct electric current
is applied to the brain via several electrodes [1]. Electrical
stimulation of primary motor cortex (M1) can modulate pain
through activation of thalamic nuclei directly connected
with motor and premotor cortices, as well as activation of
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
medial thalamus, anterior cingulate and upper brainstem
[19,33].
It has been shown that knee OA and its pain could
be associated with gray matter atrophy, reorganization in
somatosensory and motor cortex and neuroplasticity state
adjustment. These could be altered through tDCS central
effects [14]. Several recent studies have investigated the
tDCS role in the management of knee OA with promising
results [4].
Thus, beneficial effects of TENS through peripheral stim-
ulation and tDCS through cortical stimulation have been
shown in the management of knee OA but to the best of our
knowledge, no previous research has compared these two
treatment modalities. We conducted this study to investi-
gate and compare the therapeutic effects of tDCS and TENS
for the treatment of patients with knee OA.
Methods
Study design and setting
This randomized controlled trial study was a double-center
study, conducted at the Physical Medicine and Rehabilita-
tion clinic of the Shafa Yahyaian Hospital and Firoozgar
Hospital in 2019−2020. The study was approved by the
ethics committee of the Iran University of Medical Sciences
(IUMS). Research was carried out according to the Helsinki
Declaration and informed written consent was obtained
from all participants. The study was registered in the Ira-
nian Registry of Clinical Trials (#IRCT20190804044431N1;
https://www.irct.ir/trial/42,035).
Participants
Of 57 evaluated patients, 40 patients (34 females) aged
51—71 years were enrolled in this study. The inclusion cri-
teria were patients aged > 50 years with knee OA diagnosis
based on the American College of Rheumatology (ACR) cri-
teria [5]: moderate knee OA (grades II and II based on the
Kellgren-Lawrence radiologic criteria [23]), pain intensity
of ≥ 40 on visual analogue scale (VAS) while weight bear-
ing and knee pain for at least 6 months. Patients with any
neurologic and musculoskeletal disorders affecting lower
extremity function, knee joint inflammatory disorders, sec-
ondary OA, development of other knee pathology during the
study, radicular back pain, diabetes mellitus (DM), major
depressive disorder (MDD), history of knee surgery, history of
drug abuse, epilepsy, acute or chronic infection, pregnancy,
unstable conditions, electrical implants such pacemakers,
or metal implants near electrode locations were excluded.
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tDCS vs TENS in knee OA
Of 57 assessed participants, 17 subjects were not
enrolled in the study (10 due to unwillingness to partici-
pate in this study, 3 with VAS < 40, 2 with a history of knee
surgery, and 2 with a history of epilepsy).
History and demographic information were obtained from
all patients before the intervention.
Randomization, patient enrolment and blinding
40 subjects were randomly assigned to one of 2 treatment
groups, the TENS group (n = 20) or the tDCS group (n =
20), using randomly generated treatment allocations within
sealed envelopes. The physician who evaluated the outcome
measures, the participants, and the person responsible for
data analysis were all blinded to the group allocation.
Intervention
Patients in each group received 6 sessions of intervention
over a 2-week period (3 sessions per week).
In the TENS group, patients were positioned in the supine
position and the electrical current was applied to the most
painful part of the affected knee. We positioned 4 rubber
electrodes with a surface of 35 cm2 in a square pattern
around the kneecap, approximately 5 cm apart, centered
over the pain point. The treatment current was applied using
conventional TENS with the following parameters: frequency
of 100 Hz; pulse width of 100 ␮s; and intensity of 10 % below
the patient motor threshold for 25 min.
In the tDCS group, using a battery driven stimulator (Acti-
vadose II), a constant current with an intensity of 2 mA was
applied for 20 min per session through 2 rubber electrodes
with a surface of 35 cm2 and covered with 0.9 % saline soaked
sponges. The anode electrode was placed over the M1 (C3 or
C4 according to the 10—20 system of electroencephalogra-
phy electrode placement) on the hemisphere contralateral
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
this montage effective for pain alleviation in knee OA [1].
In both groups, strengthening exercises of the knee mus-
cle were taught to all participants by a physical medicine
and rehabilitation specialist. These consisted of closed chain
strengthening exercise of the quadriceps muscle (e.g. wall
squat, Forward Step-up, lunges) and patients were told to do
the mentioned exercises twice a day during the treatment
period.
Patients were advised to withhold all analgesic at
least 1 week before entering the study and to only use
acetaminophen in case of pain intensity > 60 on VAS.
Outcome measures
Patients’ symptoms and function were assessed by the Visual
Analogue Scale (VAS) and Persian version of the Western
Ontario and McMaster Universities Osteoarthritis (WOMAC)
index. All outcome measures were assessed at baseline, 1
week, 1 month and 3 months after the end of the last treat-
ment session.
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
3
Pain intensity was measured using a 100 cm VAS (0 = no
pain at all and 100 = the worst pain possible), a reliable
index for pain evaluation [7]. Patients were asked to mark
the maximum pain they had experienced in the last two days
on the VAS ruler.
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,
pain, and physical function. Answers to each of the 24
questions are scored on 5-point Likert scales (none = 0,
slight = 1, moderate = 2, severe = 3, extreme = 4), with total
scores ranging from 0 to 96. Higher scores indicate greater
disease severity. The validity and reliability of the Persian
version of WOMAC have been described by Nadrian et al. in
2012 [30].
Any adverse effect of interventions was registered.
Sample size
Sample size was calculated using the study by Chang et al.
[10]. According to this study and an alpha of 0.05, a test
power of 80 %, confidence interval of 95 % and considering a
20 % dropout, a minimum of 20 patients for each group was
calculated.
Statistical analysis
Outcome measures were analyzed using SPSS software V24.
The Kolmogorov—Smirnov test revealed normal distribution
of data, so parametric tests were used. Independent sam-
ple t-test and Chi-square test were used for analysis of
baseline characteristics. The interaction effect of time and
group on outcome measures were evaluated using mixed
ANOVA and post hoc tests (confidence interval (CI) = 95 %).
A Greenhouse-Geisser correction was used in the event of
sphericity violation. Statistical significance was considered
to be less than 0.05.
Results
During the course of the study, none of the participants
dropped out and all 40 subjects attended treatment and
follow-up sessions. Finally, 20 patients in both the TENS and
tDCS groups were analyzed. No significant differences were
observed between two treatment groups regarding demo-
graphic and patients’ baseline characteristics (Table 1).The
interaction effect of time and group was not significantly
different when evaluating VAS (df = 2.33, F = 1.35, p = 0.263)
(Fig. 1), WOMAC score (Fig. 2) and its subscales, i.e. stiff-
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-
ior of two treatment groups did not differ regarding the
changes in the course of the above-mentioned outcomes
(Table 2).
In the tDCS group, significant improvement was observed
regarding all outcomes when comparing the baseline val-
ues to follow-up evaluations (i.e. baseline to 1st follow-up,
baseline to 2nd follow-up and baseline to last follow-up). In
the TENS group, the same result was observed only in the VAS
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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
its subscales was not significant at the 1st follow-up, though
they improved significantly at second and third follow-up vs.
baseline. At the 3-month evaluation, a slight non-significant
increase was observed in the VAS (second vs third follow-
up) in both treatment groups and in WOMAC total score and
subscales of stiffness and function in TENS group, though all
these measures were significantly lower than baseline values
(Table 3).
There was no adverse effect in either group.
Discussion
This study was conducted to evaluate the efficacy of tDCS
and TENS combined with home knee strengthening exercises
in patients with knee OA. According to the findings of the
present study, both TENS and tDCS combined with exercise
improved patients’ knee pain (evaluated by VAS and WOMAC
score) and functional condition (evaluated by WOMAC score)
toward 1 month after the end of treatment and their improv-
ing effect was preserved for another 2 months. Furthermore,
the early improvement (within the first week after thera-
peutic course) in patients’ pain and function (based on the
WOMAC index) was significant only in patients who received
tDCS.
Anodal tDCS has been associated with pain reduction
in various chronic pain syndromes including fibromyalgia
[16], multiple sclerosis [29] and chronic recurrent low back
pain (CRLBP) [36]. Several recent studies have demon-
strated potential effects of tDCS with M1-SO montage in
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
techniques were associated with significant pain reduc-
tion in the first week after an 8-week period of treatment
sessions (2 sessions/week) although pain during walking
decreased two-fold in tDCS compared to sham tDCS (41.4
vs 20.7in VAS). Function measured by WOMAC improved

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 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
analysis showed no significant difference regarding their
outcome measures. Ahn et al. [2] performed tDCS with a
shorter treatment interval (5 daily sessions). They reported
better pain improvement in the tDCS group compared to
the sham group (p = 0.03). Interestingly, the pain improve-
ment effect started after the first treatment session and
it was preserved through 3-week follow-up evaluations.
Of note, though marginally better functional improvement
and mobility performance were observed with tDCS (eval-
uated by WOMAC index and 6-Minute Walk Test (6MWT),
respectively), the difference was not statistically significant
between the two treatment groups.
According to another study by Ahn et al. in 2018 [3], 5
sessions of daily M1-SO tDCS with a constant direct current
of 2 mA intensity for 20 min can reduce experimental pain
sensitivity and facilitate pain inhibition. These changes in
experimental pain measures were associated with pain alle-
viation. Another study by Ahn et al. [1] showed that daily
tDCS for 5 sessions was associated with improved mobility in
elderly patients with knee OA (a mean difference of 15.74 m
compared to sham, p = 0.105).
Historically, pain in knee OA was considered to be a
regional pain condition caused only by regional peripheral
nociceptive afferents [32]. Recent studies confirmed that
central pain sensitization has a vital role in knee OA, lead-
ing to local and widespread hyperalgesia in these patients
[15,28]. tDCS with M1-SO montage could modulate the pain
central pathways (M1-thalamic inhibitory connections) and
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
interventions such as knee exercises [31,35].
There is no consistent protocol for the management
of knee OA with tDCS. The ideal effects of tDCS could
depend on several factors including stimulation parame-
ters, treatment duration and intervals, the polarity of the
electrode, the target brain area, electrode preparation
methods and the target population [46]. Of note, 2 mA inten-
sity was associated with increased excitability under either
anode or cathode. In contrast, the 1 mA intensity resulted
in increased excitability under the anode and decreased
excitability under the cathode [3]. So, the underlying pain
reduction mechanism could alter between studies using dif-
ferent current intensity as observed in Ahn’s studies [1—4]
(2 mA tDCS) compared to Chang’s study [10] (1 mA tDCS).
Some authors have evaluated the efficiency of tDCS com-
bined with peripheral electrical stimulation (PES). Boggio
et al. [9] evaluated the combination of tDCS and TENS
in patients with chronic neurogenic pain of the arm. In
their study, all patients underwent 3 different treatments:
TENS + tDCS, sham TENS + tDCS, and Sham TENS + sham tDCS.
The treatment order was randomly selected in each patient
and there was a 48 -h interval between each session. In this
study, only early assessment was performed, i.e., immedi-
ately after the treatment session. According to their result,
significant pain alleviation was observed in two active groups
(TENS + tDCS and tDCS + sham TENS). Furthermore, the two-
fold pain reduction in the TENS + tDCS compared to other
treatment groups, was statistically significant (p = 0.02).
Hazime et al. [22] reported similar results with the com-
bined tDCS and PES in patients with CRLBP. Better analgesic
effect was observed with the tDCS + PES in the short-term
follow-up and patients’ pain improved up to 3 months only in
the tDCS + PES group. No group revealed significant improve-
ment longer-term evaluation (6-months). Furthermore, da
Graca-Tarragó et al. [14] reported that tDCS combined with
intramuscular electrical stimulation (EIMS) (5 daily sessions)
had significant additive analgesic effects with respect to
either of the two modalities in patients with knee OA.
Several hypotheses have been put forward to explain this
synergy. Schabrun et al. [36] suggested that the analgesic
effects of the two techniques could be combined for a bet-
ter outcome. Hazime et al. [22] described the metaplasticity
phenomenon. Based on this hypothesis, the combination of
an inhibitory technique (high-frequency PES at the sensory
level) with another excitatory intervention (anodal tDCS)
may increase the effectiveness of each technique via home-
ostatic plasticity [6]. Bocci et al. [8] have also demonstrated
the effect of tDCS combined with rTMS on metaplasticity of
human visual cortex.
On the other hand, Harvey et al. [21] found no addi-
tional effect for combined tDCS with TENS over TENS alone
in patients with pelvic pain.
Several side effects have been associated with tDCS in the
literature including fatigue during cranial stimulation and
reduced seizure threshold, headache, mood change, visual
changes, nausea and insomnia after the treatment session
[2]. The studies evaluating M1-SO montage in patients with
knee OA reported no or limited side effects [2,10]. Similarly,
in the present study, no adverse effect was documented.
Due to lack of adverse effects, the home use of this
modality has been utilized by some authors [4]. Further-
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
more, tDCS is considered as an effective means of provoking
sustained changes in regional neural activity [24].
In the present study, significant analgesic effect and
functional improvement were observed in patients received
TENS, in line with previous studies. Chen et al. [12]
suggested that TENS is a better treatment compared to
intra-articular injection of hyaluronic acid in patients with
knee OA. According to their result, both treatments were
associated with improved pain (evaluated by VAS) and
function (evaluated by the Lequesne index) toward the 3-
month follow-up. At the 2-week follow-up, better pain relief
and functional improvement were observed in the TENS
group; at the last follow-up session, functional improvement
was significantly greater in the TENS group. Conversely, in
Vance et al.’s study [44], active TENS was associated with
increased pressure pain threshold over the knee and tibialis
anterior muscle. However subjective pain at rest and during
movement significantly reduced in active as well as placebo
TENS.
In the meta-analyses of 14 randomized controlled tri-
als (RCT) by Chen et al. [11], a significant analgesic effect
was observed with TENS compared to control groups (mean
difference of -0.79; p < 0.01). Although a better WOMAC
score was observed in TENS groups, the difference was slight
and not statistically significant. According to the Cochrane
review by Rutjes et al. [34], a mean difference of 0.07 was
observed in VAS between TENS and control groups in favor
of the ES modality.
Many factors such as dosing, interaction with drugs, pop-
ulation, outcome measures and timing of the assessment
could influence TENS results which may explain different
results of the previous studies [39].
The present randomized clinical trial compared the
effect of tDCS with TENS on knee OA for the first time,
but the results should be interpreted in the light of several
limitations. The main limitations were a limited follow-up
period (3 months) and the lack of a sham group. Further
study with longer follow-up duration, evaluation of differ-
ent tDCS protocols and comparison of TENS + tDCS with TENS
and tDCS and sham intervention is recommended for better
evaluation of these modalities.
Conclusion
Based on the results of this study, there were no signifi-
cant differences between tDCS and TENS groups on pain and
function of patients with knee OA.
Conflicts of interest
No conflicts are declared.
Acknowledgments
This study did not receive any financial support.
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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