European Journal of Neurology 2008, 15: 1124–1130 doi:10.1111/j.1468-1331.2008.02270.

Modulatory effects of anodal transcranial direct current stimulation on

perception and pain thresholds in healthy volunteers
P. S. Boggioa,b*, S. Zaghia*, M. Lopesa and F. Fregnia
a
Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,
USA; and bPrograma de Pós-Graduação em Distúrbios do Desenvolvimento e Núcleo de Neurocieˆncias do Comportamento, Centro de
Cieˆncias Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, São Paulo, Brazil

Keywords:
brain polarization,
chronic pain, healthy
subjects, pain threshold,
transcranial direct current
stimulation
Received 14 February 2008
Accepted 2 July 2008
Background and purpose: We aimed to evaluate whether transcranial direct current
stimulation (tDCS) is effective in modulating sensory and pain perception thresholds in
healthy subjects as to further explore mechanisms of tDCS in pain relief.
Methods: Twenty healthy subjects received stimulation with tDCS under four different
conditions of stimulation: anodal tDCS of the primary motor cortex (M1), dorsolat-
eral prefrontal cortex (DLPFC), occipital cortex (V1), and sham tDCS. The order of
conditions was randomized and counterbalanced across subjects. Perception threshold
and pain threshold to peripheral electrical stimulation of the right index finger were
evaluated by a blinded rater. Results: The results showed a significant effect of the
interaction time versus stimulation condition for perception (P = 0.046) and pain
threshold (P = 0.015). Post hoc comparisons revealed that anodal stimulation of M1
increased both perception (P < 0.001, threshold increase of 6.5%) and pain
(P = 0.001, threshold increase of 8.3%) thresholds significantly, whilst stimulation of
the DLPFC increased pain threshold only (P = 0.046, threshold increase of 10.0%).
There were no significant effects for occipital or sham stimulation. Conclusions: These
results show that both M1 and DLFPC anodal tDCS can be used to modulate pain
thresholds in healthy subjects; thus, the mechanism of tDCS in modulating pain
involves pathways that are independent of abnormal pain-related neural activity.

lation on pain is that these methods of brain stimu-

Introduction
Non-invasive methods of brain stimulation, including
transcranial direct current stimulation (tDCS) and
repetitive transcranial magnetic stimulation (rTMS), are
emerging as promising techniques for the management of
pain in patients with chronic, intractable pain disorders
[1]. Several rTMS studies in chronic pain have shown
promising results (see review [1]). For example, a single
session of 10-Hz rTMS over the primary motor cortex
(M1) has been shown to transiently reduce pain levels in
patients with intractable neurogenic pain [2,3]. Recently,
tDCS has been introduced as an effective tool to ame-
liorate chronic pain. Indeed, stimulation of M1 with
tDCS has been shown to alleviate pain in patients with
traumatic spinal cord injury [4], fibromyalgia [5], and
cancer pain [6]. Nonetheless, the mechanism of these
methods on the perception of pain remains elusive at best.
Whilst the exact mechanism is unclear, the most
accepted hypothesis as to the effect of cortical stimu-
Correspondence: Felipe Fregni, Berenson-Allen Center for
Noninvasive Brain Stimulation, 330 Brookline Ave – KS 452, Boston,
MA 02215, USA (tel.: 617-667-5272; fax: 617-975-5322;
e-mail: ffregni@bidmcharvard.edu).
*Equally contributing authors.
lation function by interfering with plastic changes
associated with chronic pain. Indeed, this idea has
best been established in M1 stimulation for pain of
thalamic origin: animal studies show that transection
of the spinal cord results in burst hyperactivity of
VPL thalamic neurons that can be decreased by M1,
but not sensory cortex, stimulation [7]. Furthermore,
epidural stimulation of M1 has been found to relieve
both thalamic hyperactivity and pain in human spinal
cord injury pain patients [8]. These findings suggest
that M1 stimulation modulates abnormal thalamic
activity to relieve pain in chronic pain syndromes
[9,10].
Transcranial direct current stimulation influences the
level of cortical excitability and modulates the firing
rate of individual neurons in a polarity-dependent
fashion: anodal M1 stimulation enhances and cathodal
stimulation diminishes cortical excitability [11,12]. In
addition to affecting excitability and generating neuro-
plasticity in cortical areas directly under the electrode,
anodal tDCS has also been shown to induce effects in
distant brain areas via a connectivity-driven network
effect [13,14]. For example, anodal tDCS of M1 has
been proposed to modulate chronic pain by activating
descending inhibitory M1-thalamic projections [1].

 2008 The Author(s)

1124 Journal compilation  2008 EFNS
 Modulation of pain threshold with transcranial direct current stimulation
Whilst M1 tDCS- as well as epidural motor cortex
stimulation and rTMS- have all been shown to alleviate
intractable pain from certain chronic pain syndromes, it
is unclear whether the effects of these methods of
stimulation depend on abnormal baseline neural activ-
ity. Indeed, studies with 10-Hz rTMS reveal that the
effects of the stimulation vary widely depending on pain
site and origin [3]. Thus, it is unknown whether the
analgesic effects of tDCS may be induced via modula-
tion of normal pain-related neural networks. This is
especially important to understand for several reasons:
(i) to appreciate the mechanism by which tDCS gener-
ates a palliating effect in chronic pain, and specifically
to understand whether effective tDCS modulation relies
on a dysfunction neural network; (ii) to help determine
which types of pain syndromes may benefit the most
from methods of non-invasive brain stimulation; and
(iii) to determine whether tDCS may be indicated for
use in acute pain states (before plastic maladaptive
changes take place) or as a preventive method – before
surgery, for instance. An understanding of these prin-
ciples will help guide the applicability of tDCS treat-
ments and will allow for enhancements in the technique
of this procedure.
Thus, we decided to test the effect of tDCS on per-
ception and pain thresholds in healthy volunteers. We
chose tDCS as the method of cortical stimulation as it is
a simple yet powerfully effective method of brain
stimulation. Specifically, we conducted a double-blind
cross-over study to assess whether anodal tDCS of
different cortical areas – primary motor cortex (M1),
dorsolateral prefrontal cortex (DLPFC), and occipital
cortex (V1), (in addition to sham stimulation) – is
associated with perception and pain threshold changes
in healthy subjects.
Methods
Study design
We conducted a single-center, doubled-blinded, ran-
domized, sham-controlled, cross-over trial to determine
the effect of a single session of tDCS on pain threshold
and perception in healthy volunteers. This study con-
formed to the ethical standards of the Declaration of
Helsinki and was approved by the institutional ethics
committee at Mackenzie University, Brazil and also by
the National Ethics Committee (SISNEP, Brazil –
http://portal.saude.gov.br/sisnep/).
Subjects
Twenty healthy volunteers (mean age of 21.0 ± 2.8
years, mean ± SD; 7 men, 13 women) were recruited
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Journal compilation  2008 EFNS European Journal of Neurology 15, 1124–1130
1125
from Mackenzie University to participate in this study.
Written advertisements were posted around campus and
interested subjects contacted the study coordinator to
enroll; the study coordinator explained the risk/benefits
of the study and screened interested individuals for eli-
gibility. Subjects were regarded as suitable to participate
in this study if they fulfilled the following criteria: (1) age
between 18 and 35 years, (2) no clinically significant or
unstable medical, neuropsychiatric, or chronic pain dis-
order, (3) no history of substance abuse or dependence,
(4) no use of central nervous system-effective medication,
(5) no history of brain surgery, tumor, or intracranial
metal implantation. All subjects were interviewed and
examined by a physician prior to enrollment in the study.
All study participants provided written, informed
consent.
Experimental design
The healthy subjects received stimulation with tDCS
under each of four different conditions of stimulation:
anodal tDCS of M1, DLPFC, V1, and sham tDCS.
The order of stimulation was randomized according to
a computer algorithm that generated various permu-
tations of stimulation; participants were numbered
according to their order of entry and a randomization
list was used to assign the participants to a given order
of stimulation. Before and during each stimulation
session (after 3 min of stimulation), perception and
pain thresholds to peripheral electrical stimulation
(PES) were assessed. Each tDCS session lasted for
5 min in duration. Because short-term tDCS of 5–
7 min duration has been shown to induce transient
after-effects that return to baseline within the first
minutes after stimulation [10,15], each run was sepa-
rated by 50 min, and baseline measurements were re-
peated between trials to monitor for any long-lasting
effects.
Transcranial direct current stimulation (tDCS)
Transcranial direct current stimulation is based on the
application of a weak DC to the scalp via two relatively
large anode and cathode electrodes. During tDCS, low-
amplitude DCs penetrate the skull to enter the brain.
Although there is substantial shunting of current in the
scalp, sufficient current penetrates the brain to modify
the transmembrane neuronal potential [16,17] and,
thus, influences the level of excitability and modulates
the firing rate of individual neurons. The direction of
the cortical excitability change depends on current
orientation, such that anodal stimulation generally in-
creases cortical excitability, whilst cathodal stimulation
decreases it [11,15,18].
1126 P. S. Boggio et al.
During each session, patients received either sham
stimulation or anodal stimulation of M1, DLPFC, or
V1. A pair of surface sponge electrodes (35 cm2) were
soaked in saline and applied to the scalp at the desired
sites of stimulation. Rubber bandages were used to hold
the electrodes in place for the duration of stimulation.
For anodal stimulation of M1, the anode electrode was
placed over C3 according to the 10–20 system for EEG
electrode placement. The reference cathode electrode
was placed over the supraorbital area on the opposite
side. Similarly, for anodal stimulation of DLPFC, the
anode electrode was placed over F3 – as confirmed
reliable by neuronavigational techniques [19,20], and
the cathode electrode was placed over the contralateral
supraorbital area. For anodal stimulation of V1, the
anode electrode was placed over Oz and the cathode
electrode was placed over the contralateral supraorbital
area. For SHAM stimulation, the electrodes were
placed in the same positions as for anodal M1 stimu-
lation, but the stimulator was turned off after 30 s of
stimulation as previously described being a reliable
method of blinding [21]. In this context, it is conceivable
that in our experiment, tDCS changed activity in M1,
DLPFC, and V1, respectively, during stimulation of
these areas.
The rationale for the choice of stimulation was the
following: M1 stimulation via tDCS, rTMS, and epi-
dural stimulation have all been associated with de-
creased pain in patients with chronic pain syndromes
(see review [1]); in fact, we used the same electrode
montage as our previous tDCS studies in chronic pain
[4,5]. DLPFC was chosen as an area of stimulation
because the DLFPC is a critical part where the neural
circuit is involved in processing the cognitive and
emotional aspects of pain [22]. In addition, a previous
rTMS study showed that stimulation of this area is
associated with a reduction of pain in patients with
depression [23]. Finally, to have reliable control con-
ditions, we decided to have two control conditions: an
active condition (occipital stimulation – this was also
important to control for the effects of the reference
electrode – supraorbital contralateral electrode) and a
sham condition (in which no stimulation was delivered,
except for the first 30 s). Of note, whereas other studies
apply the reference electrode of occipital stimulation
over Cz [24,25], for this study, we felt that placement of
the reference electrode over the contralateral supraor-
bital cortex would provide a more reliable alternate
control condition.
For all active tDCS conditions, DC was delivered by
a specially developed, battery-driven, constant current
stimulator (Schneider Electronic, Gleichen, Germany)
with a maximum output of 10 mA. A constant current
of 2 mA was applied for 5 min and threshold testing
Journal compilation  2008 EFNS European Journal of Neurology 15, 1124–1130
started after 3 min of stimulation as 3 min is the min-
imum duration necessary to change cortical excitability
[11]. Perception and pain threshold testing were per-
formed during stimulation. tDCS delivered at a level of
2 mA has been shown to be safe and painless for use in
healthy volunteers [26].
Evaluations of perception threshold and pain threshold
All evaluations were performed by a blinded rater
immediately before and during each stimulation ses-
sion. The primary outcomes were perception threshold
and pain threshold to electrical stimulation. PES was
applied to the right index finger (pulse duration: 200 ls)
using a Digitimer DS-7A electrical stimulator (Hert-
fordshire, England). Current supply started at 0 mA
and was increased in steps of 0.1 mA until the subject
reported sensation and then pain. The intensity of
current at which the subject first reported perception of
the electrical stimulus was taken as the perception
threshold; the intensity of current at which the subject
reported pain was taken as the pain threshold. For each
threshold measurement, four trials were conducted and
then averaged for analysis. Our data showed that these
measurements were stable and reliable. Although other
studies use thermal pain stimulation [27] or laser-
induced pain [28] as the preferred method for deter-
mining pain threshold, PES has the benefit of allowing
a back-to-back determination of both perception and
pain thresholds within a single run.
Statistical analysis
Analyses were done with Stata Statistical Software
(version 8.0, College Station, TX, USA). To compare
the effects of stimulation on perception and pain
thresholds, we performed a mixed ANOVA model in
which the dependent variable was either the pain or
perception threshold and the independent variables
were time of evaluation (before or during stimulation),
condition of stimulation (M1, DLPFC, V1, or SHAM),
the interaction term time · condition, and the random
variable subject ID to account for the within subjects
variability. When appropriate, post hoc comparisons
were carried out using Bonferroni correction for mul-
tiple comparisons.
To assess carry-over effects, we compared baseline for
each condition of stimulation and also included the term
order (1st, 2nd, 3rd, and 4th condition of stimulation) in
our model. Unless stated otherwise, all results are pre-
sented as means and SD (means and SEM are used in the
figures – note that figures show mean and SEM of the
difference between post- and pre-treatment), and statis-
tical significance refers to a two-tailed P-value < 0.05.
 2008 The Author(s)
 Modulation of pain threshold with transcranial direct current stimulation 1127

Results

Percentage of perception threshold

9
8 *
Subjects tolerated the tDCS procedure well. There were 7

changes from baseline

no adverse effects, except for one subject who reported
headache after the end of occipital stimulation. Sensa-
tion associated with tDCS was perceived only at the
beginning of stimulation in 17 of the 20 subjects; and
these 17 participants specifically denied feeling any
sensations from tDCS during the PES threshold testing.
Three subjects reported tingling/burning sensation
throughout the entire stimulation session; interestingly,
two of these subjects also reported this same sensation
during sham stimulation. Of the 20 subjects enrolled,
only 16 participated in all four conditions of stimula-
tion. All 20 subjects completed stimulation at DLPFC,
19 completed SHAM, and 16 completed the entire 4-h
experiment undergoing stimulation at all conditions
including M1 and V1 (see Table 1).
Perception threshold
The two-way mixed ANOVA showed that the interaction
time of evaluation versus condition of stimulation was
statistically significant [F(3,76) = 2.78; P = 0.0465] for
changes to the threshold at which subjects first reported
perception of the target stimulus. Post hoc comparisons
showed a significant increase in perception threshold
after M1 stimulation only (P < 0.001, threshold in-
crease of 6.5%). There were no significant changes after
stimulation of DLFPC (P = 0.58, threshold increase of
1.2%), V1 (P = 0.91, threshold increase of 0.2%) and
sham stimulation (P = 0.44, threshold decrease of
0.3%) (see Fig. 1).
Pain threshold
Results from the two-way mixed ANOVA for pain
threshold were similar to perception threshold: there
was a significant interaction time versus group
[F(3,76) = 3.71; P = 0.015] for changes to the threshold
6
5
4
3
2
1
0
–1
–2 M1 DLPFC Occipital Sham
Figure 1 Sensory perception threshold changes (percent change
from baseline) associated with the four conditions: M1 (primary
motor cortex), DLPFC (dorsolateral prefrontal cortex), occipital
(V1), and sham tDCS. *Indicates statistically significant
(P < 0.05). Each column represents mean percentage change ±
SEM.
at which subjects first reported pain from the target
stimulus. Post hoc comparisons showed a significant
increase in pain threshold during M1 stimulation
(P = 0.001, threshold increase of 8.3%) and also dur-
ing stimulation of the DLFPC (P = 0.046, threshold
increase of 10.0%). There were no significant pain
threshold changes during V1 (P = 0.76, threshold in-
crease of 1.2%) and sham stimulation (P = 0.87,
threshold increase of 0.42%) (see Fig. 2).
Carry-over effect
To analyze carry-over effect, we initially analyzed
whether perception and pain thresholds at baseline were
similar. A one-way ANOVA in which the dependent
variable was the baseline threshold and independent
variable was condition of stimulation showed that this
variable was not significant for both perception and
pain threshold (F < 0.5 for both conditions). We then
analyzed whether there was an effect of order in our
results (including the term order in the original model).
This analysis also disclosed that the main effect of order
was not significant for both perception and pain
thresholds (F < 0.5 for both models).

Table 1 Sensory perception and pain

threshold throughout the experiment Baseline M1 Baseline DLPFC Baseline Occipital Baseline Sham

Perception threshold (mA)

Mean 2.96 3.14 2.97 3.02 2.95 2.95 2.95 2.92
SD 1.02 1.05 0.82 0.97 0.85 0.89 0.90 0.74
% Change 0.06 0.01 0.00 )0.01
Pain threshold (mA)
Mean 4.59 4.97 4.43 5.09 4.46 4.49 4.41 4.42
SD 2.44 2.64 1.98 3.21 2.09 2.01 2.30 2.31
% Change 0.08 0.13 0.01 0.00

Sensory perception and pain thresholds: mean values and percent change associated with the
four conditions: M1 (primary motor cortex), DLPFC (dorsolateral prefrontal cortex), occipital
(V1), and sham tDCS. Mean values are reported as minimum level of current applied (mA) via
PES to generate either a perception or pain response during threshold testing.

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Journal compilation  2008 EFNS European Journal of Neurology 15, 1124–1130
1128 P. S. Boggio et al.
14
*
Percentage of pain threshold
12
changes from baseline
10 * somatosensory perception and pain thresholds, it
8 should be noted that for safety reasons, the tDCS
6 electrodes have a relatively large surface area (35 cm2).
4
2 6 (premotor cortex), areas 1 and 2 of the postcentral
0 gyrus (S1 and S2) are also stimulated and may be
M1 DLPFC Occipital
Figure 2 Pain threshold changes (percent change from baseline)
associated with the four conditions: M1 (primary motor cortex),
DLPFC (dorsolateral prefrontal cortex), occipital (V1), and sham
tDCS. *Indicates statistically significant (P < 0.05). Each column
represents mean percentage change ± SEM.
Discussion
In this study, we applied anodal tDCS to different
cortical regions in healthy volunteers and compared
perception and pain thresholds that were measured
before and during stimulation. During M1 stimulation,
we measured a 6.5% increase in the threshold required
for the participants to report perception of the PES
target stimuli. Other sites of tDCS, including DLPFC
and V1, and SHAM stimulation, did not result in sta-
tistically significant changes to perception threshold. In
addition, we found that during M1 and DLPFC stim-
ulation (but not V1 or sham), the threshold required for
the healthy volunteers to report a painful sensation in
response to PES increased by 8.3% and 10.0%,
respectively. These results indicate that anodal tDCS of
M1 increases both perception and pain thresholds,
whilst anodal tDCS of DLPFC increases pain threshold
only. V1 stimulation and sham both had no effect on
either perception or pain threshold – the lack of a
placebo effect perhaps being due to the fact that the
subjects did not know that tDCS was applied with the
intention of affecting pain and perception thresholds.
Our results demonstrate that tDCS of M1 can indeed
increase pain thresholds in healthy volunteers; and
therefore, we conclude that the pain-modulating fea-
tures of anodal M1 tDCS do not require abnormal
baseline neural activity. Modulation of M1 with tDCS
has been proposed to result in the inhibition of thalamic
and brainstem nuclei activity – decreasing the hyper-
activity in these areas that underlie chronic pain [29].
Indeed, neuroimaging studies demonstrate that anodal
M1 tDCS induces widespread bi-directional changes in
regional neuronal activities including thalamic nuclei
[12]. Therefore, in these experiments, tDCS may be
modulating M1-thalamic inhibitory connections, such
that a greater magnitude of stimulus is required to
generate a perception response [1].
With respect to the effect of M1 stimulation on
Thus, whilst placement of the electrodes over M1 has
most of the effect on BroadmannÕs area 4 (M1) and area
Sham
affected by M1 stimulation [30]. Although it is true that
a smaller electrode size would result in more focal
effects, stimulation conditions were kept constant in
relation to other clinical studies with the goal of
enhancing comparability to these other tDCS studies,
namely those performed in patients with chronic pain
[4–6]. Thus, the effect of M1 anodal stimulation on the
observed increase in perception and pain threshold can
be explained as mediated primarily by action on M1 or
– less likely, but possibly – by action on the somato-
sensory cortex.
Indeed, experiments with rTMS suggest evidence in
favor of the suggestion that anodal M1 tDCS mediates
its effect on perception exclusively via stimulation of
M1: a rTMS study by Enomoto et al. suggests that
focal S1/S2 stimulation does not alter the detection of
somatosensory stimuli [31]. In addition, a tDCS study
by Antal et al. demonstrates that whilst cathodal tDCS
of S1 significantly diminished subjective pain percep-
tion, anodal and sham stimulations had no effect [28];
and, Dieckhofer et al. report that whilst cathodal tDCS
of S1 leads to a reduction of the N20 component of
SEPs, anodal stimulation results in no effect [32]. Fi-
nally, Ragert et al. show that anodal tDCS of S1 ap-
plied under slightly alternative parameters enhances
(rather than decreases) tactile spatial acuity. Together,
this evidence suggests that anodal tDCS of somato-
sensory cortex might have no effect on pain modula-
tion; therefore, any observed effects in sensory
perception during anodal M1 tDCS would more
probably be mediated by action primarily through M1.
Therefore, we propose that anodal tDCS of M1 mod-
ulates both perception and pain thresholds via corti-
cothalamic inhibition of epicritic and nociceptive
sensation at the VPL and VPM thalamic nuclei,
respectively [33].
Interestingly, our data suggest that anodal stimula-
tion of the DLPFC might have an impact on pain
modulation, but perhaps by a mechanism distinct from
M1 stimulation. This is especially pertinent because our
results indicate that anodal stimulation of DLPFC
changes pain thresholds in healthy volunteers without
generating a significant effect on perception thresholds.
It is also interesting to note that the pain threshold was
 2008 The Author(s)
Journal compilation  2008 EFNS European Journal of Neurology 15, 1124–1130
 Modulation of pain threshold with transcranial direct current stimulation
increased by a greater magnitude during DLPFC
stimulation than M1 stimulation (although this differ-
ence was not statistically significant).
The DLPFC plays an important role in anxiety,
depression [23], and unpleasantness related to pain [34].
Indeed, pain following normally non-painful heat
stimuli uniquely engages extensive areas of this part of
the brain [35]. Interestingly, the activity of DLPFC has
been shown to correlate negatively with the perception
of pain, suggesting that the DLPFC may have a
dampening effect on the activity of the midbrain-medial
thalamic pathway. Thus, the DLPFC may be activated
during painful states and may in turn ultimately mod-
ulate structures involved in the emotional perception of
pain including the anterior cingulate cortex, insula, and
amygdala [35]. Thus, tDCS of DLPFC may interfere
with the emotional processing of pain by actively
exerting control on pain perception by modulating
these corticosubcortical and corticocortical pathways
[35]. It has also been shown that 10-Hz TMS of the left
DLPFC reduces pain in patients with major depression,
further supporting this hypothesis [23].
These results ultimately suggest that M1 stimulation
produces an analgesic effect by modulating the sensory
aspects of pain, whilst DLPFC stimulation mediates its
effects by modulating affective-emotional networks
associated with pain, especially unpleasantness associ-
ated with pain. Thus, depending on the nature of the
pain, chronic pain patients may have different responses
to these two methods of stimulation. For example,
patients with chronic pain associated with spinal cord
injury might be expected to have a larger response to
M1 stimulation because of the sensory reorganization
and dysfunction present in this condition; on the con-
trary, chronic pain in major depression might benefit
more from stimulation of DLPFC. Here, it may also be
speculated that DLPFC might be the best site of stim-
ulation for chronic pain with excessively long duration
– as in this condition, affective-emotional aspects of
pain may play an especially significant role. Further-
more, it would be interesting indeed to observe the ef-
fect of simultaneous anodal M1 and DLPFC
stimulation on pain thresholds, as we propose that
synchronized stimulation of these two sites may confer
even greater increases in pain threshold than either one
alone.
One limitation that needs to be entertained is that we
used PES as our method of somatosensory stimulation
and did not assess other types of pain threshold such as
those associated with temperature- or laser-induced
pain. Because age and upper limb tension affect current
perception thresholds elicited by PES [36], it has been
suggested that electrical stimulation is not the ideal tool
for investigating pain perception. However, PES has the
 2008 The Author(s)
Journal compilation  2008 EFNS European Journal of Neurology 15, 1124–1130
1129
advantage of allowing us to determine perception and
pain thresholds within a single run, allowing for added
control in comparing the relative values and helping to
minimize habituation and sensitization induced by the
serial testing. Of note, the mean age for participants in
this study was 21.0 ± 2.8 years, and care was taken to
ensure that all subjects rested their arm comfortably
during the stimulation testing. Furthermore, whereas
laser stimuli activate Ad and C pain fibers, peripheral
electrical stimuli primarily activates Ab fibers [37]; this
feature of PES was particularly appealing because it
allowed us to study both perception thresholds and
pain thresholds via a common modality.
Our data suggest that anodal tDCS of M1 in healthy
volunteers increases both perception and pain thresh-
olds, whilst stimulation of DLPFC increases pain
thresholds only. Therefore, we conclude that the pain-
modulating features of anodal M1 tDCS do not require
abnormal thalamic activity (or an otherwise dysfunc-
tional neural network), and we suggest that stimulation
of DLPFC may modulate pain via a mechanism distinct
from M1 stimulation. In addition to contributing to the
understanding of potential mechanisms for the action
of tDCS in chronic pain, our results open new avenues
to be explored in further studies – such as simultaneous
anodal M1 and DLPFC stimulation.
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 2008 The Author(s)