High-Intensity Interval Training (HIIT) and Transcranial Direct Current Stimulation (tDCS) in Women With Fibromyalgia - Effects on Clinical and Neuro-physiological Variables: Randomized Clinical Trial Protocol
Phase: NA
Conditions: Fibromyalgia (FM)
Sponsor: Universidad Nacional Andres Bello

Exercise and Neuromodulation in Women with Fibromyalgia: 
Neurophysiological Adaptations and Clinical Effects 
 
 
Unique Protocol Id: 33B2024 
Date of Document: 14/10/2024 
Sponsor: Universidad Andrés Bello 
Principal Investigator: Edith Elgueta Cancino 
 
 
 
 

Study Protocol: Exercise and Neuromodulation in Women with 
Fibromyalgia: Neurophysiological Adaptations and Clinical Effects 
 
 
INTRODUCTION 
Fibromyalgia (FM) is the third most common musculoskeletal condition among 
unspecific chronic pain conditions with a prevalence of 2.7% worldwide1 and a ratio female 
to male 3:12. FM is characterized by three cardinal symptoms1: widespread pain (i.e. 
generalized head-to-toes 1 and neuropathic symptoms such as paraesthesia 3 4), fatigue 
(physical and mental) and sleep disorders (insomnia, frequent awakening, non-restoring 
sleep) 1 5-7. 
 
Several non-pharmacological treatments are available for managing FM symptoms 
such as (i) patient education, (ii) psychotherapy, (iii) neuromodulation (transcranial direct 
current stimulations: tDCS) and (iv) exercise 1. The exercise has shown effective for reduce 
pain, fatigue and improves functionality in fibromyalgia8. The Ottawa expert panel 
recommends aerobic exercise as a treatment for individuals with fibromyalgia 9. Similarly, 
the European League Against Rheumatism 10 exercise has strong recommendation as well; 
specifically, aerobic exercise has a moderate effect size to reduce pain and to improve 
physical function 11. Bush et al. (2002) 12 was conducted to examine the effects of aerobic 
exercise training in FM, reporting reduction in pain levels (11.4%), pain pressure threshold 
(28.1%) and improves aerobic performance (17.1%) 12. Despite the positive results of 
exercise interventions, the effect of moderate intensity exercise is small 13 and the adherence 
of these exercise programs is variable, with a treatment dropouts between 5%-34%14.  
 
 
Among the strategies to enhance these metrics, various components of physical 
training have been analyzed, including frequency, duration, type of exercise, and intensity. 
Interesting, the intensity can play an important role in modulating pain and fatigue 15. In 
healthy subjects, has been reported high-intensity interval training (HIIT) generates positive 
effects in the physical performance, such as increase in maximum strength, muscle power 
and lean mass 16. HIIT can modulate the corticospinal excitability, generates exercise 
enjoyment and increases opioids release in comparison to moderate intensity continuous 
aerobic exercise 17-19. These three components can play an important role in increasing 
exercise adherence. Regarding FM, there are two studies that have shown HIIT decrease pain, 
anxiety, depression and improves functional capacity, sleep quality and QoL15 20.  
 
 
On the other hand, exercise has limitations such as muscle soreness and fatigue, which 
are described as common physiological effects of initial training in individuals who are 
deconditioned. Another alternative that has been shown to be effective for modulation of pain 
in FM, is neuromodulation through transcranial Direct Current Stimulation (tDCS). The 
tDCS has been shown to increase endogenous μ-opioids release in chronic pain 21 and in 
healthy subjects improves the muscle endurance 22. The exercise and tDCS have shown 
effectiveness in management on pain, fatigue, sleep, anxiety, depression, and quality of life 
15 20 23-26. This suggests the tDCS effects are complementary to exercise 23. However, further 
research is needed to confirm these findings, due to the lack of evidence about combined 
effects of HIIT and tDCS in FM. We hypothesized HIIT + tDCS will be more effective in 

the modulating on clinical and neurophysiological variables in comparison than HIIT + sham 
and HIIT alone. 
 
OBJECTIVES 
Primary objective 
The study aims to compare the effectiveness HIIT + tDCS, HIIT + sham tDCS and HIIT 
alone in reducing pain in women with FM. 
 
Secondary objective 
o To identify changes after training HIIT + tDCS, HIIT + sham tDCS and HIIT alone on pain, 
clinical and neurophysiological variables.  
o To determine the association between pain, clinical and neurophysiological variables of HIIT + 
tDCS, HIIT + sham tDCS and HIIT alone. 
 
MEHTODS AND ANALYSIS 
Trial design 
This protocol is reported following the Standard Protocol Items: Recommendations for 
Interventional Trials Guide27. This is a single centre, 3 arm factorial randomized clinical trial 
(RCT). The participants will be randomized by age and intensity of pain (moderate-severe) 
using a random blocked randomization sequence after pre intervention measurements. We 
will use a 1:1:1 allocation ratio to HIIT + tDCS, HIIT + sham tDCS and HIIT. Other 
investigator of staff will be carried out the randomization and sequentially numbered sealed 
envelopes process.  
Only one investigator responsible for all assessments and training sessions will be 
blinded to tDCS intervention. The volunteers will not be blinded to tDCS. 
 
 
Study setting 
This is a single site study. All procedures will be carried out at the Musculoskeletal 
Laboratory, Andrés Bello University.  
Eligibility criteria 
Inclusion criteria: will include women between 18-65 years old with a diagnosis of 
Fibromyalgia by physician according to the criteria of the American College of 
Rheumatology (ACR) 2016. Stable medical treatment for symptoms for a least 4 weeks prior 
to participation, reported pain equal or higher than 4/10 on numeric rating pain scale 
(moderate or severe pain) for more than 3 months, body mass index (BMI) between 18.5 and 
39.9 kg m-2, stable doses medication for ≥4 weeks, Central Sensitization inventory ≥40 
points, controlled high blood pressure.  
 
Exclusion criteria: Present pain unrelated to Fibromyalgia (isolated inflammatory joint, 
cancer, infectious, traumatic, localized neuropathic or degenerative joint pain), intense 
headache, cerebral surgery, seizure/epilepsy, cardiovascular, lung, metabolic (II diabetes 
mellitus), retinopathy or neurological diseases (i.e. stroke and traumatic brain injury 
antecedents), severe psychiatric disorders, medication contraindicated by TMS, have a 
cochlear-ferromagnetic and cardiac pacemaker, drugs and alcohol abuse. Are currently 
pregnant/breastfeeding, under physical therapy treatment or have participated in a designed 

sports or exercise training in systematic programs previous 3 months. Are unable to speak or 
read Spanish fluently (inability to understand the pain scale and cooperate in testing). 
 
 
INTERVENTION 
Exercise 
HIIT familiarization 
The participants will perform a physical conditioning protocol that includes two weeks with 
three times per week 28 of HIIT 80%-95% of maximum heart rate (HR) 20  in the following 
way: 
TIME 
INTERVAL 
PASSIVE 
RECOVERY 
SESSIONS 
maximum 
HR 
15 s 
2 
2 min 
2 
80%-95% 
30 s 
3-5 
2 min 
2 
80%-95% 
45 s 
5-7 
2 min 
2 
80%-95% 
Table 1. Description of HIIT familiarization. 
 
HIIT training 
From the seventh session to the eighteenth, the participants will perform a HIIT protocol that 
consists of 1 minute of active cycling at 80%-95% maximum HR 20, 2 minutes of passive 
recovery for 10 times (1x2x10). Moreover, during HIIT training, will be monitored the effort 
of HIIT session through RPE scale (6-20) 29 at 15-18 RPE 30 31 between 50-60 revolutions 
per minute (“workload it costs to pedal, neither light nor heavy”), HR and pain at the 
beginning and end of each cycle of HIIT. If the participant fails to recover within 2 minutes 
(>70% maximum heart rate), longer rest time will be allowed until ≤ 70% of maximum HR 
is achieved 28. The maximum HR of each session will be considered the maximum HR for 
the HIIT prescription for the next session. In addition, the diet will be controlled with respect 
to the day before and the day of exercise session. 
 
Transcranial direct current stimulation (tDCS) 
Over the course of four weeks, the tDCS will be applied at the same time as the HIIT session 
(during exercise). The individual will receive a total of 12 tDCS sessions. 
 
Active (anodal) tDCS 
The anode will be placed on the left M1 and the cathode on contralateral supraorbital area 
before the exercise starts. The stimulation will start at the same time the start exercise 
intervention, with an intensity of 2mA for 20 minutes 32. 
 
Sham tDCS 
During exercise intervention, to replicate the feeling of current ramping up during active 
stimulation, the active anode placed on the left M1 will be activated for 30 seconds at the 
beginning and end of the procedure 33. A period of 30 seconds of ramping is reliable for 
blinding 34. Evidence shows that a time period of less than 3 minutes of tDCS intervention, 
does not generates cortical excitability changes 33. 
 
Outcomes  

Primary clinical outcome 
The primary outcome is the Numeric rating scale (0-10). Commonly used to assess pain 
severity using a 0–10 scale, with zero meaning “no pain” and 10 meaning “the worst pain 
imaginable” 35.  
Secondary clinical outcomes 
The other cardinal symptoms in fibromyalgia are fatigue and sleep alterations. The fatigue 
will be assessed through the Multidimensional Fatigue Inventory (MFI)36. Sleep will be 
assessed through VAS (0-100mm)37 and Pittsburgh Sleep Quality Index (PSQI)38.  
Also, women with fibromyalgia suffer in psychosocial features and will be evaluated 
catastrophizing of pain through Pain Catastrophizing Scale (PCS)39, fear of movement 
through The Tampa Scale for Kinesiophobia (TSK)40-42, anxiety through State Trait Anxiety 
Inventory (STAI)43 and depression through Beck’s Depression Inventory II (BDI-II)44 45. The 
cardinal symptoms and psychosocial features affect the QoL. Will be evaluated the QoL 
through Fibromyalgia Impact Questionnaire (FIQ)46 and Short Form 3647.  
Regarding exercise, will be evaluated the Three-repetition sit-to-stand test (3R-STS) to 
quantify the muscle soreness before training sessions, the individuals will be asked to sit and 
stand 3 times with their legs shoulder width apart and bend their knees to 90° 48 by the VAS 
pain (0-100 mm). The VAS pain is a validated, subjective measure for acute and chronic 
pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a 
continuum between “no pain” and “worst pain” 49. The volunteers must mark with a straight 
vertical line on the horizontal line. Moreover, will be assessed exercise adherence through 
Exercise Attitude Questionnaire-18 (EAQ-18) 50 51, exercise enjoyment through Physical 
Activity Enjoyment Scale (PACES)52 53, physical level activity through International 
Physical Activity Questionnaire (IPAQ)54 and cardiovascular risk through Physical Activity 
Readiness Questionnaire (PAR-Q)55, the perception of effort during the exercise by Borg’s 
Scale 56 and dyspnoea57 58. Finally, will be assessed the anthropometric characteristics 
through InBody 770 (Sout Korea) and the heigh by stadiometer.  
Secondary neuro-physiological outcomes 
The corticospinal excitability will be measured with transcranial magnetic stimulation using 
a Magstim 2002 & a 7 mm double cone coil (Magstim, UK) in combination with surface 
electromyography (sEMG; Delsys Bagnoli 16 channels, USA) (supplementary information 
10). The stimulation will be in left M1 cortex, and the EMG recordings will be gathered in 
right vastus lateralis muscle using Ag/AgCl electrodes. The specific variables that will be 
assessed are: 
 
Motor Evoked Potential (MEP): is the response of the muscle to the stimulation of the 
corticomotor pathway and it is frequently used to estimate corticospinal excitability 59. It can 
be measured as the peak-to-peak amplitude of the EMGs signal. The average of 15 MEPs 
peak-to-peak amplitudes using an intensity of 120% active motor threshold (aMT) will be 
collected to asses CSE 60 61. 
 
Cortical Silent Period (CSP): The CSP is defined as the  “temporary interruption of 
electromyographic signal from muscle following a MEP” 62. It is considered a measure of 
the excitability mediated by gamma-aminobutyric acid (GABAB) receptors (GABABR). The 
SP will be measured in milliseconds (ms) from the end of the MEP wave to the recovery 
EMG signal to the basal averaged amplitud 63 64. 
 

Rest Motor Threshold (rMT, % output): rMT is defined as the lowest stimulus intensity to 
evoke MEPs with a peak-to-peak amplitude of 50μV in at least five out of 10 consecutive 
trials when the muscle at rest 65. rMT will be expressed as percentage of the TMS output. 
 
Active Motor Threshold (aMT, % output): it is the lowest intensity of the stimulator needed 
to evoke MEPs with a peak-to-peak amplitude of ≥200 µV in five out of 10 consecutive trials 
while maintaining an isometric contraction at 10% of the maximal voluntary contraction 
(MVC)66. aMT will be expressed as percentage of the TMS output. 
 
Short Interval intracortical Inhibition (SICI) and Intracortical Facilitation (ICF): Both are 
transient phenomena that occur at the motor cortex, SICI is a suppression or reduction of the 
firing of cortical neurons - GABAA inhibitory circuits- 67-69 and ICF is an excitatory 
phenomenon mediated by N-methyl-D-aspartate receptors (NMDAR)  70. Paired pulse 
paradigms will be used to assess both. These paradigms involve two consecutive 
stimulations, one conditioning stimulus that is below the threshold (80% rMT) followed by 
a test stimulus that is above the threshold (120% of the motor threshold) 32. To assess short 
intracortical inhibition (SICI), the interstimulus interval will be set to 2 ms, while for 
intracortical facilitation (ICF), the interval will be set to 15 ms 32. We will administer ten 
random stimuli at each interval and calculate the percentage of inhibition or facilitation 
before and after treatment 32.  
 
Others neuro-physiological outcomes will be assessed are pain pressure threshold by 
algometer in bilateral supraspinatus muscle, lateral epicondyle, gluteus area and medial fat 
knee according ACR 1990 71 72, aerobic capacity 73, quadriceps strength of dominant leg by 
maximal voluntary isometric contraction (MVIC) 74 and endurance muscle contraction by a 
time to exhaustion of knee extensors (20% MVIC) adding to High density electromyography 
(HD-sEMG) for motor units recruitment  75-77. 
 
STATISTICAL ANALYSIS PLAN 
 
Study sample 
Will include women between 18-65 years old with a diagnosis of Fibromyalgia by physician 
according to the criteria of the American College of Rheumatology (ACR) 2016. We will 
enroll 40 volunteers divided into 3 groups. 
 
Sample size calculation 
The sample size was calculated using G*Power 3.1 (Germany), based on the variable pain 
measured by the Visual Analogue Scale (VAS) from the study by Kolak et al. (2022)78 with 
a power of 0.80, an alpha level of 0.05, and accounting for a 20% dropout rate, the required 
sample size was determined a total of n=40. 
 
Statistical Analysis  
The distribution of the data for all variables will be corroborated with the Shapiro wilk 
normality test. Two-way ANOVA and Pearson correlation will be used if the data is normally 
distributed, considering a p value < 0.05. If no normal distribution is found the data will be 
transformed or nonparametric analysis will be used. The data will be presented as mean and 
standard deviation. Moreover, Two-way ANCOVA will be performed. 

 
Ethics and dissemination 
This protocol was approved by the scientific ethics committee (number: 33B2024) at the 
Faculty of Medicine, Andres Bello University. The results will be reported in congress and 
peer review journal. 
 
 

REFERENCES 
1. Sarzi-Puttini P, Giorgi V, Marotto D, et al. Fibromyalgia: an update on clinical 
characteristics, 
aetiopathogenesis 
and 
treatment. 
Nat 
Rev 
Rheumatol 
2020;16(11):645-60. doi: 10.1038/s41584-020-00506-w [published Online First: 
2020/10/08] 
2. Queiroz LP. Worldwide epidemiology of fibromyalgia. Current pain and headache 
reports 2013;17:1-6. 
3. Koroschetz J, Rehm SE, Gockel U, et al. Fibromyalgia and neuropathic pain-differences 
and similarities. A comparison of 3057 patients with diabetic painful neuropathy and 
fibromyalgia. BMC neurology 2011;11(1):1-8. 
4. Rehm SE, Koroschetz J, Gockel U, et al. A cross-sectional survey of 3035 patients with 
fibromyalgia: subgroups of patients with typical comorbidities and sensory symptom 
profiles. Rheumatology 2010;49(6):1146-52. 
5. Sandıkçı SC, Özbalkan Z. Fatigue in rheumatic diseases. European Journal of 
Rheumatology 2015;2(3):109. 
6. Kleinman L, Mannix S, Arnold LM, et al. Assessment of sleep in patients with 
fibromyalgia: qualitative development of the fibromyalgia sleep diary. Health and 
quality of life outcomes 2014;12:1-11. 
7. Bennett RM, Jones J, Turk DC, et al. An internet survey of 2,596 people with fibromyalgia. 
BMC musculoskeletal disorders 2007;8(1):1-11. 
8. Geneen LJ, Moore RA, Clarke C, et al. Physical activity and exercise for chronic pain in 
adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev 
2017;4(4):CD011279. doi: 10.1002/14651858.CD011279.pub3 [published Online 
First: 2017/04/25] 
9. Brosseau L, Wells GA, Tugwell P, et al. Ottawa Panel evidence-based clinical practice 
guidelines for aerobic fitness exercises in the management of fibromyalgia: part 1. 
Phys Ther 2008;88(7):857-71. doi: 10.2522/ptj.20070200 [published Online First: 
2008/05/24] 
10. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the 
management of fibromyalgia. 
Ann Rheum 
Dis 2017;76(2):318-28. doi: 
10.1136/annrheumdis-2016-209724 [published Online First: 2016/07/06] 
11. Busch AJ, Barber KA, Overend TJ, et al. Exercise for treating fibromyalgia syndrome. 
Cochrane database of systematic reviews 2008(4) 
12. Busch A, Schachter CL, Peloso PM, et al. Exercise for treating fibromyalgia syndrome. 
Cochrane Database Syst Rev 2002(3):CD003786. doi: 10.1002/14651858.CD003786 
[published Online First: 2002/07/26] 
13. Hauser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in 
fibromyalgia syndrome: a systematic review and meta-analysis of randomised 
controlled trials. Arthritis Res Ther 2010;12(3):R79. doi: 10.1186/ar3002 [published 
Online First: 2010/05/13] 
14. Sarmento CV, Liu Z, Smirnova IV, et al. Exploring Adherence to Moderate to High-
Intensity Exercises in Patients with Fibromyalgia: The Role of Physiological and 
Psychological Factors—A Narrative Literature Review. Physiologia 2023;3(3):472-
83. 
15. Bodéré C, Cabon M, Woda A, et al. A training program for fibromyalgia management: 
A 5-year pilot study. SAGE Open Medicine 2020;8:2050312120943072. 

16. Caparrós-Manosalva C, Garrido-Muñoz N, Alvear-Constanzo B, et al. Effects of high-
intensity interval training on lean mass, strength, and power of the lower limbs in 
healthy old and young people. Frontiers in Physiology 2023;14 
17. Saanijoki T, Tuominen L, Tuulari JJ, et al. Opioid release after high-intensity interval 
training in healthy human subjects. Neuropsychopharmacology 2018;43(2):246-54. 
18. Thum JS, Parsons G, Whittle T, et al. High-intensity interval training elicits higher 
enjoyment 
than 
moderate 
intensity 
continuous 
exercise. 
PloS 
one 
2017;12(1):e0166299. 
19. Hendy AM, Andrushko JW, Della Gatta PA, et al. Acute effects of high-intensity aerobic 
exercise on motor cortical excitability and inhibition in sedentary adults. Frontiers in 
Psychology 2022;13:814633. 
20. Atan T, Karavelioğlu Y. Effectiveness of high-intensity interval training vs moderate-
intensity continuous training in patients with fibromyalgia: a pilot randomized 
controlled 
trial. 
Archives 
of 
Physical 
Medicine 
and 
Rehabilitation 
2020;101(11):1865-76. 
21. DosSantos MF, Love TM, Martikainen IK, et al. Immediate effects of tDCS on the μ-
opioid system of a chronic pain patient. Frontiers in psychiatry 2012;3:93. 
22. Cogiamanian F, Marceglia S, Ardolino G, et al. Improved isometric force endurance after 
transcranial direct current stimulation over the human motor cortical areas. European 
Journal of Neuroscience 2007;26(1):242-49. 
23. Mendonca ME, Simis M, Grecco LC, et al. Transcranial direct current stimulation 
combined with aerobic exercise to optimize analgesic responses in fibromyalgia: a 
randomized placebo-controlled clinical trial. Frontiers in human neuroscience 
2016;10:68. 
24. Teixeira PE, Pacheco-Barrios K, Branco LC, et al. The analgesic effect of transcranial 
direct current stimulation in fibromyalgia: a systematic review, meta-analysis, and 
meta-regression of potential influencers of clinical effect. Neuromodulation: 
Technology at the Neural Interface 2023;26(4):715-27. 
25. Hou W-H, Wang T-Y, Kang J-H. The effects of add-on non-invasive brain stimulation 
in fibromyalgia: a meta-analysis and meta-regression of randomized controlled trials. 
Rheumatology 2016;55(8):1507-17. 
26. Couto N, Monteiro D, Cid L, et al. Effect of different types of exercise in adult subjects 
with fibromyalgia: a systematic review and meta-analysis of randomised clinical 
trials. Scientific Reports 2022;12(1):10391. 
27. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: 
guidance for protocols of clinical trials. Bmj 2013;346 
28. Cano-Montoya J, Álvarez C, Martínez C, et al. Recuperación cardiovascular durante 
ejercicio intermitente en pacientes con hipertensión y diabetes tipo 2 altamente 
adherentes. Revista médica de Chile 2016;144(9):1150-58. 
29. Abbiss CR, Peiffer JJ, Meeusen R, et al. Role of ratings of perceived exertion during self-
paced exercise: what are we actually measuring? Sports medicine 2015;45:1235-43. 
30. Taylor JL, Holland DJ, Spathis JG, et al. Guidelines for the delivery and monitoring of 
high intensity interval training in clinical populations. Progress in cardiovascular 
diseases 2019;62(2):140-46. 
31. Taylor JL, Bonikowske AR, Olson TP. Optimizing outcomes in cardiac rehabilitation: 
the importance of exercise intensity. Frontiers in Cardiovascular Medicine 
2021;8:734278. 

32. Castelo-Branco L, Kucukseymen EU, Duarte D, et al. Optimised transcranial direct 
current stimulation (tDCS) for fibromyalgia—targeting the endogenous pain control 
system: a randomised, double-blind, factorial clinical trial protocol. BMJ open 
2019;9(10) 
33. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak 
transcranial direct current stimulation. The Journal of physiology 2000;527(Pt 3):633. 
34. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for 
double-blind sham-controlled clinical studies in brain stimulation. Clinical 
neurophysiology 2006;117(4):845-50. 
35. Breivik H, Pc B. Allen sm, et al. Assessment of pain Br J Anaesth 2008;101:17-24. 
36. Munguía-Izquierdo D, Segura-Jiménez V, Camiletti-Moirón D, et al. Multidimensional 
Fatigue Inventory: Spanish adaptation and psychometric properties for fibromyalgia 
patients. The Al-Andalus study. Clin Exp Rheumatol 2012;30(Suppl 74):94-102. 
37. Martin S, Chandran A, Zografos L, et al. Evaluation of the impact of fibromyalgia on 
patients' sleep and the content validity of two sleep scales. Health and Quality of Life 
Outcomes 2009;7:1-7. 
38. Hita-Contreras F, Martínez-López E, Latorre-Román PA, et al. Reliability and validity 
of the Spanish version of the Pittsburgh Sleep Quality Index (PSQI) in patients with 
fibromyalgia. Rheumatology international 2014;34:929-36. 
39. Campayo JG, Rodero B, Alda M, et al. Validación de la versión española de la escala de 
la catastrofización ante el dolor (Pain Catastrophizing Scale) en la fibromialgia. 
Medicina Clinica 2008;131(13):487-92. 
40. Roelofs J, Goubert L, Peters ML, et al. The Tampa Scale for Kinesiophobia: further 
examination of psychometric properties in patients with chronic low back pain and 
fibromyalgia. European Journal of Pain 2004;8(5):495-502. 
41. Burwinkle T, Robinson JP, Turk DC. Fear of movement: factor structure of the Tampa 
Scale of Kinesiophobia in patients with fibromyalgia syndrome. The Journal of pain 
2005;6(6):384-91. 
42. Gómez-Pérez L, López-Martínez AE, Ruiz-Párraga GT. Psychometric properties of the 
Spanish version of the Tampa Scale for Kinesiophobia (TSK). The journal of Pain 
2011;12(4):425-35. 
43. Spielberger CD, Gorsuch RL, Lushene RE. Cuestionario de ansiedad estado-rasgo. 
Madrid: Tea 1982;1 
44. Sanz J, Perdigón A, Vázquez C. The Spanish adaptation of Beck’s Depression Inventory-
II (BDI-II): 2. Psychometric properties in the general population. Clínica y Salud 
2003;14(3):249-80. 
45. Beck AT, Steer RA, Brown G. Beck depression inventory–II. Psychological assessment 
1996 
46. Salgueiro M, García-Leiva JM, Ballesteros J, et al. Validation of a Spanish version of the 
revised fibromyalgia impact questionnaire (FIQR). Health and quality of life 
outcomes 2013;11(1):1-8. 
47. Monterde S, Salvat I, Montull S, et al. Validación de la versión española del Fibromyalgia 
Impact Questionnaire. Rev esp reumatol(Ed impr) 2004:507-13. 
48. Aldayel A, Jubeau M, McGuigan MR, et al. Less indication of muscle damage in the 
second than initial electrical muscle stimulation bout consisting of isometric 
contractions of the knee extensors. European journal of applied physiology 
2010;108:709-17. 

49. Delgado DA, Lambert BS, Boutris N, et al. Validation of digital visual analog scale pain 
scoring with a traditional paper-based visual analog scale in adults. Journal of the 
American Academy of Orthopaedic Surgeons Global research & reviews 2018;2(3) 
50. Arturi P, Schneeberger EE, Sommerfleck F, et al. Adherence to treatment in patients with 
ankylosing spondylitis. Clinical rheumatology 2013;32:1007-15. 
51. Manigandan C, Charles J, Divya I, et al. Construction of exercise attitude questionnaire-
18 to evaluate patients’ attitudes toward exercises. International Journal of 
Rehabilitation Research 2004;27(3):229-31. 
52. Motl RW, Dishman RK, Saunders R, et al. Measuring enjoyment of physical activity in 
adolescent girls. American journal of preventive medicine 2001;21(2):110-17. 
53. Moreno J-A, González-Cutre D, Martínez C, et al. Propiedades psicométricas de la 
Physical Activity Enjoyment Scale (PACES) en el contexto español. Estudios de 
Psicología 2008;29(2):173-80. 
54. Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 
12-country reliability and validity. Medicine & science in sports & exercise 
2003;35(8):1381-95. 
55. Baechle TR, Earle R, Baechle TR. NSCA's essentials of personal training: Human 
Kinetics 2004. 
56. Borg G. Borg's perceived exertion and pain scales: Human kinetics 1998. 
57. Crisafulli E, Clini EM. Measures of dyspnea in pulmonary rehabilitation. 
Multidisciplinary respiratory medicine 2010;5:1-9. 
58. Inostroza M, Valdés O, Tapia G, et al. Effects of eccentric vs concentric cycling training 
on patients with moderate COPD. European journal of applied physiology 2022:1-
14. 
59. Klomjai W, Katz R, Lackmy-Vallee A. Basic principles of transcranial magnetic 
stimulation (TMS) and repetitive TMS (rTMS). Ann Phys Rehabil Med 
2015;58(4):208-13. doi: 10.1016/j.rehab.2015.05.005 [published Online First: 
2015/09/01] 
60. Ridding M, Taylor J. Mechanisms of motor‐evoked potential facilitation following 
prolonged dual peripheral and central stimulation in humans. The Journal of 
physiology 2001;537(2):623-31. 
61. Bement MKH, Weyer AD, Yoon T, et al. Corticomotor excitability during a noxious 
stimulus before and after exercise in women with fibromyalgia. Journal of Clinical 
Neurophysiology 2014;31(1):94-98. 
62. Zeugin D, Ionta S. Anatomo-functional origins of the cortical silent period: spotlight on 
the basal ganglia. Brain sciences 2021;11(6):705. 
63. Hupfeld K, Swanson C, Fling B, et al. TMS-induced silent periods: A review of methods 
and call for consistency. Journal of neuroscience methods 2020;346:108950. 
64. Cacchio A, Cimini N, Alosi P, et al. Reliability of transcranial magnetic stimulation-
related measurements of tibialis anterior muscle in healthy subjects. Clinical 
neurophysiology 2009;120(2):414-19. 
65. Pacheco-Barrios K, Lima D, Pimenta D, et al. Motor cortex inhibition as a fibromyalgia 
biomarker: A meta-analysis of transcranial magnetic stimulation studies. Brain 
network and modulation 2022;1(2):88. 
66. Groppa S, Oliviero A, Eisen A, et al. A practical guide to diagnostic transcranial magnetic 
stimulation: report of an IFCN committee. Clin Neurophysiol 2012;123(5):858-82. 
doi: 10.1016/j.clinph.2012.01.010 [published Online First: 2012/02/22] 

67. Kujirai T, Caramia M, Rothwell JC, et al. Corticocortical inhibition in human motor 
cortex. The Journal of physiology 1993;471(1):501-19. 
68. Ziemann U, Lönnecker S, Steinhoff B, et al. Effects of antiepileptic drugs on motor cortex 
excitability in humans: a transcranial magnetic stimulation study. Annals of 
Neurology: Official Journal of the American Neurological Association and the Child 
Neurology Society 1996;40(3):367-78. 
69. Ziemann U, Rothwell JC, Ridding M. Interaction between intracortical inhibition and 
facilitation in human motor cortex. The Journal of physiology 1996;496(3):873-81. 
70. Wagle‐Shukla A, Ni Z, Gunraj CA, et al. Effects of short interval intracortical inhibition 
and intracortical facilitation on short interval intracortical facilitation in human 
primary motor cortex. The Journal of physiology 2009;587(23):5665-78. 
71. Kosek E, Ekholm Ja, Nordemar R. A comparison of pressure pain thresholds in different 
tissues and body regions. Long-term reliability of pressure algometry in healthy 
volunteers. Scandinavian journal of rehabilitation medicine 1993;25(3):117-24. 
72. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 
criteria for the classification of fibromyalgia. Arthritis & Rheumatism: Official 
Journal of the American College of Rheumatology 1990;33(2):160-72. 
73. Hooten WM, Smith JM, Eldrige JS, et al. Pain severity is associated with muscle strength 
and peak oxygen uptake in adults with fibromyalgia. Journal of pain research 
2014:237-42. 
74. Martinez-Valdes E, Falla D, Negro F, et al. Differential motor unit changes after 
endurance or high-intensity interval training. Med Sci Sports Exerc 2017;49(6):1126-
36. 
75. Angius L, Pageaux B, Hopker J, et al. Transcranial direct current stimulation improves 
isometric time to exhaustion of the knee extensors. Neuroscience 2016;339:363-75. 
76. Bouillard K, Jubeau M, Nordez A, et al. Effect of vastus lateralis fatigue on load sharing 
between quadriceps femoris muscles during isometric knee extensions. Journal of 
neurophysiology 2014;111(4):768-76. 
77. Martinez-Valdes E, Laine C, Falla D, et al. High-density surface electromyography 
provides reliable estimates of motor unit behavior. Clinical Neurophysiology 
2016;127(6):2534-41. 
78. Kolak E, Ardıç F, Fındıkoğlu G. Effects of different types of exercises on pain, quality 
of life, depression, and body composition in women with fibromyalgia: A three-arm, 
parallel-group, randomized trial. Archives of Rheumatology 2022;37(3):444.