Pain Res Manag Vol 18 No 6 November/December 2013e101
Reduction of pain thresholds in fibromyalgia after very
low-intensity magnetic stimulation: A double-blinded,
randomized placebo-controlled clinical trial
Ceferino Maestú PhD1,2, Manuel Blanco MD1,3, Angel Nevado PhD4,5, Julia Romero MD3, Patricia Rodríguez-Rubio MD3,
Javier Galindo MD3, Juan Bautista Lorite MD3, Francisco de las Morenas MD3, Pedro Fernández-Argüelles MD6
1Humanism and Science Foundation; 2Centre for Biomedical Technology, Technical University of Madrid, Madrid; 3Sagrado Corazón Hospital, Seville;
4Laboratory for Cognitive and Computational Neuroscience, Centre for Biomedical Technology, Technical University of Madrid and Complutense
University of Madrid; 5Basic Psychology Department II, Complutense University of Madrid, Madrid; 6Virgen del Rocio Hospital, Seville, Spain
Correspondence: Dr Ceferino Maestú, Centro de Tecnología Biomédica (CTB), Campus de Montegancedo, 28223 Pozuelo de Alarcón, Madrid,
Spain. Telephone 34-91452-4900 ext 24655, fax 34-91336-6828, e-mail email@example.com
physiology and behaviour. EMF have been shown to affect the synaptic
activity of snail single neurons (1) and the neuronal activity in rat hippo-
campal slice preparations (2). Analgesic effects of EMF on snails (3), mice
(4,5) and rats (6) have also been described. Although exposure of animals
to low-intensity magnetic fields has typically been performed in the µT
range, amplitudes in the nT range in electromagnetically shielded
environments (7) have also been shown to affect nociception in mice. In
humans, the effect of EMF on pain severity has also been investigated in a
variety of conditions (8) including fibromyalgia (9,10).
Fibromyalgia syndrome (FMS) is characterized by chronic wide-
spread musculoskeletal pain, fatigue, nonrestorative sleep, and concen-
tration and memory deficits (11,12). The prevalence of fibromyalgia is
approximately 2.0% in both sexes, 3.4% among women and 0.5%
among men (13). Studies of experimentally induced pain demonstrate
here is increasing evidence of the effect of low-intensity electro-
magnetic fields (EMF) on different aspects of animal and human
that these patients have a lower pain threshold because lower-intensity
stimuli are needed to evoke pain (14). The decrease in pain threshold is
particularly evident at a number of ‘tender points’ (11). Serotonin levels
in blood have also been found to be altered in FMS (15). The efficacy of
current pharmacological treatments of FMS is limited (16).
Although the precise pathophysiological basis of the disease
remains to be elucidated, recent studies have demonstrated altered
brain processing of nociceptive information in FMS patients (17,18),
which may result from hyperexcitability of the central nervous sys-
tem (19-21). Functional magnetic resonance imaging studies have
shown an increased brain response in areas activated by painful
stimuli, the amount of stimulation necessary to activate these areas
in fibromyalgia patients being lower than in healthy individuals (19).
Electroencephalographic components evoked by nociceptive stimuli
have higher amplitude and longer duration (22), and habituation
responses to repetitive stimuli are delayed in FMS patients (23).
©2013 Pulsus Group Inc. All rights reserved
C Maestú, M Blanco, A Nevado, et al. Reduction of pain thresholds
in fibromyalgia after very low-intensity magnetic stimulation:
A double-blinded, randomized placebo-controlled clinical trial. Pain
Res Manag 2013;18(6):e101-e106.
BACkgRouNd: Exposure to electromagnetic fields has been reported to
have analgesic and antinociceptive effects in several organisms.
oBjeCtive: To test the effect of very low-intensity transcranial mag-
netic stimulation on symptoms associated with fibromyalgia syndrome.
Methods: A double-blinded, placebo-controlled clinical trial was per-
formed in the Sagrado Corazón Hospital, Seville, Spain. Female fibromyal-
gia patients (22 to 50 years of age) were randomly assigned to either a
stimulation group or a sham group. The stimulation group (n=28) was
stimulated using 8 Hz pulsed magnetic fields of very low intensity, while
the sham group (n=26) underwent the same protocol without stimulation.
Pressure pain thresholds before and after stimulation were determined
using an algometer during the eight consecutive weekly sessions of the
trial. In addition, blood serotonin levels were measured and patients com-
pleted questionnaires to monitor symptom evolution.
Results: A repeated-measures ANOVA indicated statistically signifi-
cant improvement in the stimulation group compared with the control
group with respect to somatosensory pain thresholds, ability to perform
daily activities, perceived chronic pain and sleep quality. While improve-
ment in pain thresholds was apparent after the first stimulation session,
improvement in the other three measures occurred after the sixth week.
No significant between-group differences were observed in scores of
depression, fatigue, severity of headaches or serotonin levels. No adverse
side effects were reported in any of the patients.
CoNClusioNs: Very low-intensity magnetic stimulation may repre-
sent a safe and effective treatment for chronic pain and other symptoms
associated with fibromyalgia.
key Words: Analgesic effect; Fibromyalgia; Low intensity; Transcranial
la réduction des seuils de douleur en
fibromyalgie après une stimulation magnétique
de très faible intensité : un essai aléatoire
clinique à double insu contrôlé contre placebo
histoRiQue : L’exposition aux champs électromagnétiques a des effets
analgésiques et antinociceptifs sur plusieurs organismes.
oBjeCtiF : Vérifier l’effet d’une stimulation magnétique transcrânienne de
très faible intensité sur les symptômes associés au syndrome fibromyalgique.
MÉthodologie : Les chercheurs ont effectué un essai clinique à double
insu contrôlé contre placebo à l’hôpital Sagrado Corazón de Séville, en
Espagne. Les patientes atteintes de fibromyalgie (de 22 à 50 ans) ont été
réparties de manière aléatoire entre un groupe de stimulation et un groupe
témoin. Le groupe de stimulation (n=28) a été stimulé au moyen de champs
magnétiques de 8 Hz de très faible intensité, tandis que le groupe témoin
(n=26) a subi le même protocole sans stimulation. Les seuils de pression à la
douleur avant et après la stimulation ont été déterminés au moyen d’un
algomètre pendant les séances de huit semaines consécutives de l’essai. De
plus, les taux de sérotonine dans le sang ont été mesurés et les patients ont
rempli des questionnaires pour vérifier l’évolution des symptômes.
RÉsultAts : Des mesures de variance répétées ont démontré une amé-
lioration statistiquement significative du groupe de stimulation par rapport
au groupe témoin à l’égard des seuils de douleur somatosensorielle, de la
capacité d’effectuer les activités quotidiennes et de la qualité du sommeil.
Même si l’amélioration du seuil de douleur était apparente après la pre-
mière séance de stimulation, les trois autres mesures se sont améliorées au
bout de la sixième semaine. Les chercheurs n’ont observé aucune différence
significative entre les groupes pour ce qui est des indices de dépression, de
fatigue, de gravité des céphalées ou des taux de sérotonine. Aucun patient
n’a déclaré d’effets secondaires indésirables.
CoNClusioNs : Une stimulation magnétique de très faible intensité
peut représenter un traitement sécuritaire et efficace de la douleur chro-
nique et d’autres symptômes associés à la fibromyalgie.
Maestú et al
Pain Res Manag Vol 18 No 6 November/December 2013e102
A number of studies have shown that high-intensity repetitive
transcranial magnetic stimulation (TMS) can be effective for the
treatment of FMS (24-28). Marlow et al (29) conducted a review of
these and transcranial direct current stimulation studies. Conventional
repetitive TMS induces peak magnetic fields in the order of 1 T to 3 T.
The use of very low-intensity TMS, as in the present clinical trial,
which was in the order of nT, is less well researched. A previous clin-
ical trial (10) reported improvement in subjective pain scores in fibro-
myalgia patients after low-intensity magnetic stimulation using a
specific protocol, which approached statistical significance compared
with sham stimulation. In the present clinical trial, a new method of
very low-intensity TMS was used.
The present double-blinded clinical trial was designed to test the
effect of very low-intensity TMS on several symptoms associated
with FMS. Objectively measured variables were pain thresholds to
somatosensory stimulation and blood serotonin levels. In addition,
participants completed questionnaires rating levels of fatigue, anx-
iety, depression, chronic pain, sleep quality and ability to perform
Subjects were informed about the nature of the study verbally and
using printed leaflets, and informed consent was obtained from all
participants. The protocol was approved by the Ethics Committee of
Virgen Macarena Hospital (Seville, Spain) and by the Spanish Drug
and Sanitary Product Agency (Agencia Española del Medicamento y
Producto Sanitario [AEMPS], www.aemps.es/en/, trial number 275/06/
EC), and conformed to the Declaration of Helsinki. The AEMPS also
approved the final report of the clinical trial, titled Prueba de concepto
de eficacia y seguridad de la estimulación magnética de baja intensidad sobre
la enfermedad fibromiálgica (Proof of concept for the efficacy and secur-
ity of low-intensity magnetic stimulation in fibromyalgia). A double-
blinded experimental design was used, such that neither the patients
nor the experimenters knew which of the groups was being stimulated.
Inclusion criteria included the following: patients had received a diag-
nosis of fibromyalgia according to the criteria of the American
Association of Rheumatology such that they experienced widespread
pain and tenderness at 11 or more of 18 specific tender point sites;
patients had to have been diagnosed at least 12 months before the
beginning of the clinical trial; and patients had to be female (because
fibromyalgia is more prevalent in women) and between 20 and
60 years of age. Exclusion criteria were the following: currently preg-
nant; having been diagnosed with a medical condition other than
FMS; or using a pacemaker or other metal implant, to avoid potential
heating. Patients diagnosed with other medical conditions were
excluded to minimize the possibility that potential treatment-related
symptom changes were associated with a condition that was not fibro-
myalgia. Patients were asked to discontinue any medication except,
possibly, acetaminophen or bromazepam, one month before the start of
the trial. Patients for whom this was not possible were excluded from
the study. Blood tests measuring blood cell count, acute phase react-
ants, erythrocyte sedimentation rate, serum electrolyte levels, glycemic
index, liver and thyroid function, and a number of antibodies were
performed before the trial. Results had to be normal or negative for
patients to be included in the study. Patients were recruited from mem-
bers of fibromyalgia associations in the Seville area, and evaluated for
eligibility by three experienced physicians from March to May 2006 at
the Sagrado Corazón Hospital (Seville, Spain). To obtain a sample size
that was as large as possible, all patients who accepted the invitation
to participate in the clinical trial during the predefined recruitment
period were assessed for eligibility. A total of 161 female patients were
recruited and assessed for eligibility. Of these, 67 patients fulfilling the
inclusion and exclusion criteria agreed to participate and, following a
parallel design, were randomly assigned to either the stimulation group
(n=34) or the sham group (n=33), with a 1:1 allocation ratio. Four
externally identical stimulation devices (two of which were capable of
producing magnetic fields and two of which were manipulated so that
no field was produced) were provided to the notary before randomiza-
tion. A public notary performed the 1:1 random allocation, randomly
labelled each stimulation device with the letter of the group they cor-
responded to (either A or B) and sealed them. Neither the experi-
menters nor the patients had access to the results of the randomization
until all trial outcome measures had concluded. The individuals
responsible for delivering the actual and sham stimulation knew which
group the patients belonged to, but not which group was actually being
stimulated. Of the 67 patients who were originally assigned to groups,
28 patients in the stimulation group and 26 in the sham group com-
pleted the stimulation/sham protocol (Figure 1). Therefore, data from
28 patients from the stimulation group and 26 patients in the sham
group were used for the analysis.
The selected patient group had a mean (± SD) age of 40.7±6.7 years
(range 22 to 50 years). The mean weight was 60±9.3 kg (range 47 kg
to 83 kg) and the mean height was 1.67±0.08 m (range 1.50 m to
1.75 m). All patients lived in or near Seville, in southern Spain. Of
this group, 18 (33.3%) had at least a first-degree relative diagnosed
Stimulation sessions occurred between June and August of 2006 at
the Sagrado Corazón Hospital, Seville. No adverse side effects were
reported by any of the patients throughout the course of the clinical
trial, nor did they report experiencing any somatosensory, auditory or
other sensory phenomena as a result of the stimulation.
Stimulation/sham sessions occurred once per week for eight consecu-
tive weeks. Sessions were scheduled in the morning between 09:00 and
12:00, and lasted 20 min. They occurred inside two Faraday cages to
reduce environmental electromagnetic interference. One Faraday cage
was used for actual stimulation and the other for sham stimulation. As
described, all stimulation devices were externally identical. Neither
patients nor researchers knew which was which. Stimulation was
delivered via a custom-built magnetic stimulator (30). Briefly, a flex-
ible electroencephalography (EEG) cap with 33 stimulation coils was
placed over the patient’s head. The stimulation coils were distributed
evenly in an attempt to maximize the distance between the EEG elec-
trodes, arranged according to the 10–20 system (31), to enable the
possibility of performing EEG recordings while stimulation was being
Figure 1) Patient flow diagram specifying patient numbers for each of the
Magnetic stimulation in fibromyalgia
Pain Res Manag Vol 18 No 6 November/December 2013e103
performed in future studies. Therefore, stimulation was general rather
than focal. Figure 2 shows the locations and appearance of the stimula-
tion coils. Each coil had seven loops and was 2 cm in diameter. A
digital electronic generator fed the same oscillating current of inten-
sity to the 27 coils. The current amplitude was 545 µA. Each coil
produces a magnetic field of approximately 43 nT at a distance of 1 cm
and 0.9 nT at a distance of 4 cm. A low-frequency (8 Hz) square func-
tion was used. This frequency was chosen because pilot data suggested
that it could be effective for treating fibromyalgia. Figure 3 shows a
ocilloscope measurement of the voltage applied to the coils. A fre-
quencimeter registered an applied frequency of 8.00005 Hz, which is
very close to the intended frequency. Figure 3 shows that the relative
fluctuations in voltage (noise) around the theoretical square function
to be applied were approximately 3%. The present stimulation device
differed from the protocol used by Thomas et al (10) in that stimula-
tion was less localized and signals were stationary (see Discussion for
It should be noted that very low-intensity magnetic stimulation
was used. Unlike high-intensity TMS, this stimulation system does not
produce any noise. No perceptible effects other than potentially the
main and secondary effects object of investigation were reported by
either patients or researchers.
The primary outcome measures were the pain thresholds at 18 sensi-
tive (tender) points, which were determined using an algometer before
and after each of the eight weekly stimulation sessions. Pain thresh-
olds, measured in units of pressure (kg/cm2), were obtained by con-
tinuously increasing the pressure exerted by the algometer until the
patient reported that it was starting to feel painful. The median pain
threshold value across the 18 sensitive points was subsequently calcu-
lated. Secondary outcome measures were blood serotonin levels and
self-reported ratings of specific symptoms. Serotonin levels were meas-
ured in blood before week 1 and after weeks 4 and 8. The rest of the
variables were measured using a self-reported questionnaire in which
patients rated on a visual analogue scale (ranging from 0 to 10) how
they felt the previous week with respect to the following items: ability
to perform daily activities, perceived chronic pain intensity, fatigue,
anxiety, depression, sleep quality and severity of headaches. The ques-
tionnaire was adapted from the Fibromyalgia Impact Questionnaire
(32). The ability to perform daily activities comprised nine different
questionnaire items: shopping; doing the laundry; preparing meals;
doing the washing-up; vacuum-cleaning; making the bed; going
upstairs; visiting a friend; and looking after plants. The overall ability
to perform daily activities was established by calculating the median
score across tasks. Similarly, sleep quality comprised two questionnaire
items: how good their sleep was and how they felt in the morning. Pain
thresholds were chosen as the primary outcome because the fact that
values are read from an algometer by a researcher makes them less
subjective than self-reporting questionnaires.
The different scores were introduced into a two-way repeated-
measures ANOVA. Time (weeks) × group (actual and sham stimula-
tion) interactions were considered. Time × group interactions were
evaluated globally by taking into account the entire time period of
eight weeks. In addition, the interaction term for individual weeks
was evaluated post hoc by comparing each timepoint with the values
before week 1. Statistically significant interaction terms indicate
that the time-dependant evolution for the stimulation group was
significantly different from the sham group. In the figures, variables
for which the interaction term was significant (P<0.05) globally
for the entire time-period are indicated with an asterisk (*) in the
title and are framed with a thicker line. Individual weeks for which
the evolution from values before week 1 was significantly different
between actual and sham stimulation (P<0.05) have the correspond-
ing value for the stimulation curve depicted in red; otherwise, they
are shown in black. Although the post hoc analysis is not warranted
for variables that showed no significant differences at the global
level, the same convention is used for all measures for illustrative
purposes. The analysis was performed using in-house MATLAB soft-
ware (Mathworks, USA).
The evolution of pain thresholds is presented in Figure 4. When the
entire time period of eight weeks was considered, the increase in pain
threshold was significantly larger for the stimulation group (P=0.01).
At the level of individual timepoints, all timepoints showed signifi-
cant differences, with the exception of four instances corresponding to
baseline (before treatment began) and before stimulation at weeks 2,
4 and 8. In general, no significant between-group differences were
found at baseline for any of the obtained measures, as expected from a
random allocation into sham and stimulation groups. For all figures,
curves indicate the mean and error bars indicate the SEM across
Significant global improvement in the ability to perform daily
activities (P=0.03) and sleep quality (P=0.04), and a decrease in per-
ceived pain (P=0.02) were also observed (Figure 5) when comparing
the two groups. Analysis of individual weeks indicated that these
changes occurred after week 6 for the three variables. No significant
global changes were found for fatigue, anxiety and depression scores
Figure 2) The left panel indicates the location of the stimulation coils (black
circles) in relation to the electroencephalography 10–20 system. The right
panel shows details of three coils (red) around an electroencephalography
Figure 3) Oscilloscope capture of the voltage applied to the coils. Dotted
lines indicate 0.5 V. The reading of approximately 1.2 V corresponds to an
applied current of 1.2 V/2200 Ω = 545 µA
Maestú et al
Pain Res Manag Vol 18 No 6 November/December 2013e104
No significant changes in severity of headaches at week 8 and
serotonin levels at week 4 or 8 were found (Figure 6)
Finally, to obtain an estimate of the effect size, the evolution of
pain threshold scores and subjective chronic pain ratings were re-
expressed in terms of relative changes (Figure 7). Relative changes
were defined as the difference in score between the timepoint con-
sidered and the first timepoint, divided by the score at the first time-
point. After week 8, there was a mean increase of 28% (95% bootstrap
CI 8% to 51%) across patients in pain thresholds in the stimulation
group, compared with a −10% change (95% bootstrap CI −29% to
9%) in the sham group. The change in perceived chronic pain after
eight sessions was −39% (95% bootstrap CI −51% to −29%) for the
stimulation group, compared with −8% (95% bootstrap CI −26% to
13%) in the sham group. Relative changes for other variables are
reported in Table 1.
Fibromyalgia is a prevalent condition that significantly affects the
quality of life of patients. Current treatment options exhibit limited
efficacy. In the present clinical trial, we investigated whether very low-
intensity TMS helps to reduce symptoms. The evolution of pain
thresholds during the eight-week period of the trial indicates that very
low-intensity TMS was effective in increasing the abnormally low
pain thresholds associated with FMS. Improvement in the stimulation
group occurred after the first session and was present for most of the
eight-week period. After week 6, patients also reported a decrease in
subjective chronic pain, an increase in the ability to perform daily
activities and an improvement in sleep quality. In contrast, symptoms
for which no significant differences were found included fatigue, anx-
iety and depression scores, severity of headaches and level of serotonin
The mechanisms by which central nervous exposure to weak elec-
tromagnetic fields may have analgesic and antinociceptive effects
remain to be elucidated. There is evidence that endogenous opioid
systems are affected by magnetic fields (33). Proposed mechanisms of
how weak magnetic fields may affect the central nervous system
include induced electric currents, magnetite, radical pair combina-
tions and resonance interactions (34-36). The induction of electric
currents appears to be an unlikely mechanism given that the induced
fields are orders of magnitude lower than the endogenous electric fields
present in tissues. Similarly, an important limitation of the magnetite
hypothesis is that a connection between magnetite and the nervous
system has not been demonstrated. The model most consistent with
Figure 5) Equivalent visual scale scores. Curves indicate the mean and
error bars indicate the SEM across patients. Variables for which the time ×
group interaction was significant (P<0.05) for the entire time period are
highlighted with an asterisk (*) in the title and are framed with a thicker line
(ability to perform daily activities [P=0.03], sleep quality [P=0.04] and
perceived pain [P=0.02]). No significant global changes were found for
fatigue, anxiety and depression scores. Individual weeks for which the evolu-
tion from values before week 1 was significantly different between actual and
sham stimulation (time × group interaction P<0.05) have the corresponding
bar for the stimulation curve depicted in red; otherwise they are shown in
Figure 6) Severity of headaches and serotonin level. Curves indicate the
mean and error bars indicate the SEM across patients. No significant chan-
ges (time × group interaction) in severity of headaches at week 8 and sero-
tonin levels at week 4 or 8 were observed
Figure 7) Relative changes in pain thresholds and subjective chronic pain
ratings. Evolution of pain ratings in term of relative changes with respect to
week 1. The corresponding absolute values are reported in Figure 4 and 5,
respectively. Curves indicate the mean and error bars indicate the SEM
across patients. On the time axis, B denotes baseline (before start of treat-
ment) and a and b indicate time instants before and after treatment, respect-
ively, for each week
Figure 4) Evolution of pain thresholds. The increase in pain threshold is
significantly larger for the stimulation group compared with the control group
(time × group interaction, P=0.01) when the entire time period of eight
weeks was considered. Individual weeks for which the evolution from values
before week 1 was significantly different between actual and sham stimula-
tion (P<0.05) have the corresponding value for the stimulation curve
depicted in red; otherwise they are shown in black. Curves indicate the mean
and error bars indicate the SEM across patients. On the time axis, B denotes
baseline (before start of treatment) and a and b indicate time instants before
and after treatment, respectively, for each week
Magnetic stimulation in fibromyalgia
Pain Res Manag Vol 18 No 6 November/December 2013e105
the observed effects of magnetic fields is the interaction between the
external magnetic fields and internal resonant systems such as radical
pair processes (36).
A previous clinical trial (10) investigated the effect of low-intensity
magnetic stimulation on the reduction of self-reported chronic pain
scores in fibromyalgia patients. Results indicated an improvement in
pain scores that approached statistical significance (P=0.06). While the
general approach and design is similar, differences exist between this
previous clinical trial and the present trial. In the present study, group
differences were significant (P<0.05), while in the previous study they
were approaching significance (P=0.06). In the present clinical trial,
magnetic fields were applied once per week for 20 min for eight consecu-
tive weeks, and intensity was in the order of nT. In the previous study,
patients underwent two daily sessions of 40 min for seven consecutive
days, and the magnetic fields had an intensity in the order of µT. It
should be noted, nevertheless, that this same group (7) reported noci-
ceptive effects of magnetic fields in the order of nT in mice when they
were immersed in an electromagnetically shielded environment, as in
the present study. Here, stimulation coils were evenly distributed across
the cap, while previously a more focal source was used and, therefore,
the field was less homogeneous. Finally, a square wave signal was used in
the present study, while a signal with a more complex temporal pattern
was used in the previous trial. Despite these differences, both trials pro-
vide evidence of improvement of pain scores after low-intensity TMS,
even if in the previous work the difference was marginally significant
(P<0.06). The fact that these two studies were performed independently
and with somewhat differing methodology reinforces the notion that
low-intensity TMS can be effective in alleviating the symptoms associ-
ated with FMS.
An important question for future studies is what combination of
methods/parameters is most effective in reducing FMS symptoms. It has
been reported that spatial inhomogeneities in the magnetic field
increase its analgesic effect in mice (36). Likewise, the specific temporal
pattern of stimulation, including refractory periods, has been argued to
play an important role in the effect of stimulation (37). In the present
study, coils in the stimulation device were evenly spaced across the cap
and the same stimulation parameters were used for all coils. The signals
used were square waves of a given frequency. Future studies could inves-
tigate the effect of stimulating with different spatial and temporal pat-
terns. Another important aspect concerns the duration and interval
between stimulation sessions. While in the present study stimulation
sessions lasted 20 min and occurred once per week for eight consecutive
weeks, in the Thomas et al study (10), two daily 40 min sessions for
seven consecutive days were used. Despite the comparatively long inter-
val between sessions, the increase in pain thresholds in the present study
was maintained from week to week, except for the period between
week 1 and week 2 (Figure 5, upper panel). In fact, the pain threshold
increase was roughly sustained for the eight-week trial except for a drop
at week 2 and a smaller drop at week 6; therefore, the need for a shorter
interval between stimulation sessions is not immediately obvious from
the data. Nevertheless, a shorter interval between sessions may produce
a larger increase in pain threshold if effects from different sessions are
additive. In fact, the decrease in ongoing pain is more gradual, evolving
at least until week 7. This suggests that the neurophysiological mechan-
isms underlying both types of pain are being affected differently. An
alternative explanation, given that the score for chronic pain is subject-
ive, is that patients take some time to internalize changes in symptoms.
The other scores that improved with stimulation above a possible pla-
cebo effect (ability to perform daily activities and sleep quality; Figure 5),
which are also rated subjectively, also improved in a gradual manner. All
three of these subjective scores show improvement after week 6, which
suggests that decreasing the number of sessions may reduce the benefi-
cial effect of stimulation.
The main limitation to the present trial was that no follow-up
period was included; therefore, it is not possible to establish at present
how lasting the beneficial effects of stimulation were. In addition, only
female patients from the Andalucia region (southern Spain) were
included. Future studies should include follow-up periods and male
patients to check for potential differences in responses. We do not
expect the regional distribution to have a noticeable effect in the
present results because the presentation of fibromyalgia is similar
Neuroimaging studies (19-21) have provided evidence that central
system processing of nociceptive signals is affected in FMS. The fact that
low-intensity TMS had an effect on symptoms further supports this
notion. In fact, Thomas et al (10) found that effects of stimulation were
specific to FMS because symptoms of chronic localized musculoskeletal
or inflammatory pain patients did not improve after exposure.
Future studies could investigate how changing parameters, such as
stimulation duration, interval between sessions, spatiotemporal pattern
of stimulation, number of sessions and homogeneity of magnetic fields,
affect stimulation efficacy. Further work that includes a follow-up period
is also needed to determine how long the improvement in symptoms
lasts after the stimulation sessions are discontinued.
Results from the present clinical trial show that very low-intensity
TMS can have an analgesic and antinociceptive effect when applied
to fibromyalgia patients. In addition, improvements in sleep quality
and the ability to perform daily activities were also apparent. No
adverse effects were reported. Very low-intensity magnetic stimulation
may be of benefit for the treatment of chronic pain and other symp-
toms associated with fibromyalgia, although further research is needed
to optimize stimulation parameters.
souRCes oF FuNdiNg: The authors thank the Humanism and
Science Foundation (Guzman el Bueno 66, 28015 Madrid, Spain) for
financial support. Angel Nevado received funding from project PSI2010-
22118 from the Spanish Ministry of Science and Innovation.
disClosuRes: Ceferino Maestú is an author of a patent for the mag-
netic stimulation device used in the present study.
1. Calvo AC, Azanza MJ. Synaptic neurone activity under applied 50 Hz
alternating magnetic fields. Comp Biochem Physiol C Pharmacol
Toxicol Endocrinol 1999;124:99-107.
2. Bawin SM, Satmary WM, Jones RA, Adey WR, Zimmerman G.
Extremely-low-frequency magnetic field disrupt rhythmic slow activity in
rat hippocampal slices. Bioelectromagnetics 1996;17:388-95.
3. Prato FS, Kavaliers M, Thomas AW. Extremely low frequency
magnetic fields can either increase or decrease analgesia in the land
snail depending on field and light conditions. Bioelectromagnetics
4. Choi YM, Joeng JH, Kim JS, Lee BC, Je HD, Sohn UD. Extremely low
frequency magnetic field exposure modulates the diurnal rhythm of the
pain threshold in mice. Bioelectromagnetics 2003;24:206-10.
Relative changes from baseline and 95% CIs after eight
weeks for all measured outcomes
6 to 51
−9 to 34
−50 to −28
−45 to −19
−46 to −15
−58 to −30
16 to 133
−51 to −18
−37 to 27
−30 to 9
−45 to −8
−25 to 12
−27 to 13
−31 to 13
−37 to 9
−15 to 74
−44 to −10
−33 to 30
Data presented as % unless otherwise indicated.
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5. Shupak NM, Hensel JM, Cross-Mellor SK, Kavaliers M, Prato FS,
Thomas AW. Analgesic and behavioural effects of a 100 T specific
pulsed extremely low frequency magnetic field on control and
morphine treated CF-1 mice. Neurosci Lett 2004;354:30-3.
6. Bao X, Shi Y, Huo X, Song T. A possible involvement of beta-
endorphin, substance P, and serotonin in rat analgesia induced by
extremely low frequency magnetic field. Bioelectromagnetics
7. Prato FS, Desjardins-Holmes D, Keenliside LD, et al. The detection
threshold for extremely low frequency magnetic fields may be below
1000 nT-Hz in mice. Bioelectromagnetics 2011;32:561-9.
8. Sartucci F, Bonfiglio L, Del Seppia C, et al. Changes in pain
perception and pain-related somatosensory evoked potentials in
humans produced by exposure to oscillating magnetic fields.
Brain Res 1997;769:362-6.
9. Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS,
Thomas AW. Exposure to a specific low frequency magnetic field:
A double-blind placebo-controlled study of effects on acute pain
ratings in rheumatoid arthritis and fibromyalgia pain populations.
Pain Res Manag 2006;11:85-92.
10. Thomas AW, Graham K, Prato FS, et al. A randomized, double-
blind, placebo-controlled clinical trial using a low-frequency
magnetic field in the treatment of musculoskeletal chronic pain.
Pain Res Manag 2007;12:249-58.
11. Wolfe FW, Smythe HA, Yunas MB, et al. The American College of
Rheumatology 1990 criteria for the classification of fibromyalgia.
Arthritis Rheum 1990;33:160-72.
12. Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet
survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord
13. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence
and characteristics of fibromyalgia in the general population.
Arthritis Rheum 1995;38:19-28.
14. Price DD, Staud R. Neurobiology of fibromyalgia syndrome.
J Rheumatol Suppl. 2005;75:22-8.
15. Mahdi AA, Fatima G, Das SK, Verma NS. Abnormality of circadian
rhythm of serum melatonin and other biochemical parameters in
fibromyalgia syndrome. Indian J Biochem Biophys 2011;48:82-7.
16. Recla JM. New and emerging therapeutic agents for the treatment
of fibromyalgia: An update. J Pain Res 2010;3:89-103.
17. Gibson SJ, Littlejohn GO, Gorman MM, Helme RD, Granges G.
Altered heat pain thresholds and cerebral event related potentials
following painful CO2 laser stimulation in subjects with
fibromyalgia syndrome. Pain 1994;58:185-93.
18. Granot M, Buskila D, Granovsky Y, Sprecher E, Neumann L,
Yarnitsky D. Simultaneous recording of late and ultra-late pain evoked
potentials in fibromyalgia. Clin Neurophysiol 2001;112:1881-87.
19. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic
resonance imaging evidence of augmented pain processing in
fibromyalgia. Arthritis Rheum 2002;46:1333-43.
20. Desmeules JA, Cedraschi C, Rapiti E, et al. Neurophysiologic
evidence for a central sensitization in patients with fibromyalgia.
Arthritis Rheum 2003;48:1420-9.
21. Burgmer M, Pogatzki-Zahn E, Gaubitz M, Wessoleck E, Heuft G,
Pfleiderer B. Altered brain activity during pain processing in
fibromyalgia. Neuroimage 2009;44:502-8.
22. Lorenz J, Grasedyck K, Bromm B. Middle and long latency
somatosensory evoked potentials after painful laser stimulation in
patients with fibromyalgia syndrome. Electroencephalogr Clin
23. Montoya P, Sitges C, García-Herrera M, et al. Reduced brain
habituation to somatosensory stimulation in patients with
fibromyalgia. Arthritis Rheum 2006;54:1995-2003.
24. Sampson SM, Rome JD, Rummans TA. Slow-frequency rTMS
reduces fibromyalgia pain. Pain Med 2006;7:115-8.
25. Passard A, Attal N, Benadhira R, et al. Effects of unilateral
repetitive transcranial magnetic stimulation of the motor cortex on
chronic widespread pain in fibromyalgia. Brain 2007;130:2661-70.
26. Carretero B, Martin MJ, Juan A, et al.Low-frequency transcranial
magnetic stimulation in patients with fibromyalgia and major
depression. Pain Med 2009;10:748-53.
27. Mhalla A, Baudic S, Ciampi de Andrade D, et al. Long-term
maintenance of the analgesic effects of transcranial magnetic
stimulation in fibromyalgia. Pain 2011;152:1478-85.
28. Short EB, Borckardt JJ, Anderson BS, et al.Ten sessions of
adjunctive left prefrontal rTMS significantly reduces fibromyalgia
pain: A randomized, controlled pilot study. Pain 2011;152:2477-84.
29. Marlow NM, Bonilha HS, Short EB. Efficacy of transcranial direct
current stimulation and repetitive transcranial magnetic stimulation
for treating fibromyalgia syndrome: A systematic review. Pain Pract
30. Maestú C, Álvarez R, del Pozo F. Transcranial stimulator for low
intensity, has series of brain stimulation coils to circulate current
that generates stimulator magnetic field, and signal flow is
generated by digital microcontroller. Patent number EP2371274 A1.
31. Jasper HH. Report of the Committee on Methods of Clinical
Examination in Electroencephalography. Electroenceph Clin
32. Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact
questionnaire: Development and validation. J Rheumatol
33. Kavaliers M, Ossenkopp KP. Opioid systems and magnetic field effects
in the land snail, Cepaea nemoralis. Biol Bull 1991;180:301-9.
34. Prato FS, Carson JJ, Ossenkopp KP, Kavaliers M. Possible
mechanisms by which extremely low frequency magnetic fields
affect opioid function. FASEB J 1995;9:807-14.
35. Engström S, Fitzsimmons R. Five hypotheses to examine the nature
of magnetic field transduction in biological systems.
36. Del Seppia C, Ghione S, Luschi P, Ossenkopp KP, Choleris E,
Kavaliers M. Pain perception and electromagnetic fields.
Neurosci Biobehav Rev 2007;31:619-42.
37. Thomas AW, Drost DJ, Prato FS. Human subjects exposed to a
specific pulsed (200 microT) magnetic field: Effects on normal
standing balance. Neurosci Lett 2001;297:121-4.