Exercise and Neuromodulation in Fibromyalgia

Generalised Fatigue: "is a profound and overwhelming, more severe, constant, and unpredictable than normal tiredness, not relieved by resting or sleep, not proportional to effort exerted, and disruptive in terms of motivation, activities, and cognition". The generalised fatigue will be assessed with:

Multidimensional Fatigue Inventory (MFI). A questionnaire with 20 items divided into 5 domains: general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation. The score range is between 4 to 20 points; a higher score indicates a greater degree of fatigue.

The Symptom Severity (SS) Score, a tool that measures the severity of symptoms like fatigue, unrefreshed sleep, and cognitive issues, along with other somatic symptoms, over the past week. Rating the severity from 0 (no problem) to 3 (severe).

Fibromyalgia Impact Questionnaire (FIQR): The sub-item evaluates fatigue with a rating scale of 11 blocks (0 to 10). Higher scores indicate no energy.

The sleep quality will be measured with:

Numeric Rating Scale (0-10): single-item tool that instructs the patient to describe the quality of sleep during the past 24 hours, where 0 is the best possible sleep and 10 is the worst possible sleep.

The sleep quality will be measured with:

Pittsburgh Sleep Quality Index (PSQI): a questionnaire that assesses duration, disturbance, latency, daytime dysfunction due to sleepiness, sleep efficiency, overall sleep quality and sleep medication use. Each component is scored from 0 to 3. Low scores indicate good sleep quality and high scores indicate poor sleep quality. (0-4: Good sleep quality; 5-10: Poor sleep quality; >10: Very poor sleep quality).

Depression will be assessed with two the subitem for depression of the "Fibromyalgia Impact Questionnaire (FIQR)". This goes from 0 to 10 in an 11-point rating scale with higher scores representing severity.

Beck's Depression Inventory II (BDI-II): a 21-item self-reported measure that assesses the cognitive, affective, and neurovegetative symptoms of depression. The total score is 63 points. The range score is 0-13 "minimal", 14-19 "mild", 20-28 "moderate" and 29-63 "severe".

Quality of life will be assessed with the "Fibromyalgia Impact Questionnaire (FIQR)", which is a 21-item self-administered questionnaire. The questionnaire has 3 domains: function, overall impact and symptoms. The total score ranges from 0 to 100 points; higher scores indicate a severe impact.

Quality of life will be assessed with the "Short Form-36 (SF-36)". This questionnaire surveys health status, assesses physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health. The highest score is 100, and the higher the score, the better the quality of life.

To estimate corticospinal excitability peak-to-peak amplitude of the Motor Evoked Potential (MEP) will be measured. MEP is the response of the muscle to the stimulation of the corticomotor pathway with a magnetic stimulator and is measured with electromyography in milliAmpere (mA).

The adherence to exercise will be measured by the "Exercise Attitude Questionnaire". The score is 1 point "strongly disagree", 2 points "somewhat disagree", 3 points "somewhat agree", 4 points "strongly agree". The total score is 72 points, and the cut-off point for adherence is >60 points

Physical Activity Readiness Questionnaire (PAR-Q): pre-participation screening tool for detection of possible health and cardiovascular problems. Include seven health-related questions to be answered yes or no. If the answer is "yes" to one question, the participant should talk to a physician before starting physical activity. If all questions are yes, the participant is fit to perform physical activity.

International Physical Activity Questionnaire (IPAQ): estimates the level of physical activity in different activity domains such as occupational, transport, yard/garden, household, leisure, and sitting. 27 items give a detailed picture of activity in different domains (work, transport, domestic, leisure). Measures frequency (days/week) and duration (minutes/day) of physical activity in the last 7 days, across intensity levels. It expresses activity in Metabolic Equivalent of Task (MET)-minutes per week (MET-min/week) or the energy cost of physical activities, where 1 MET is the energy expended at rest ≈ 3.5 mL O₂/kg/min. Higher values indicate greater physical activity level.

It is the maximal voluntary effort of isometric contraction. The strength of the quadriceps will be evaluated during 3 trials using an isokinetic dynamometer (Isoforce®).

A knee extension at 20% maximal voluntary contraction will be performed until exhaustion. Participants' perception of effort will be measured using the 15-point rating of perceived exertion (RPE) scale every 20 seconds of the time to exhaustion task.

The aerobic capacity will be measured during an incremental cycling test. During this test, will be determined the maximum oxygen consumption (VO2peak) and the production of maximum concentric power (POmax)

Pressure will be applied at an increasing rate of 50 kPa per second with an algometer placed perpendicular over the skin until the sensation of pressure changes to pain also known as pain pressure threshold (PPT).

To quantify the muscle soreness, the participants must mark with a straight vertical line on the horizontal line (from 0 to 100 millimetres), after performing a task of sitting and standing 3 times.

The participant will report the number of painful areas of the body (upper, lower, or axial regions) over the last week. The total score is 19, where 1 region pain equals 1 point, divided by the left upper region, right upper region, axial region, left lower region and right lower region.

It is the lowest stimulus intensity of a transcranial magnetic stimulator to generate a motor evoked potential with a peak-to-peak amplitude of 200 microvolts in at least five out of 10 consecutive trials when the muscle is activated at 20% of the maximal voluntary contraction.

It is the lowest stimulus intensity of a transcranial magnetic stimulator to generate a motor evoked potential with a peak-to-peak amplitude of 50 microvolts in at least five out of 10 consecutive trials when the muscle is at rest.

It is the temporary interruption of the electromyographic signal from a muscle following a motor evoked potential. It is considered a measure of the excitability mediated by gamma-aminobutyric acid receptors. It will be measured in milliseconds (ms) from the end of the motor evoked potential wave to the recovery of the signal to the basal averaged amplitude.

Changes in anxiety will be assessed with the subitem that evaluates anxiety of the "Fibromyalgia Impact Questionnaire (FIQR)" with 11 blocks (0 to 10), where higher scores indicate a severe impact.

State Trait Anxiety Inventory (STAI) will be used to assess anxiety levels. The total score is 80 points. The score is classified as 20-37 "no or low anxiety", 38-44 "moderate anxiety" and 45-80 "high anxiety".

The enjoyment of exercise will be assessed with the "Physical Activity Enjoyment Scale". This scale includes 16 items with a maximum score of 80 points. The rating scale ranges from 1 ("dislike a lot") to 5 ("enjoy a lot").

The participants will be asked to sit and stand 3 times with their legs shoulder-width apart and bend their knees to 90°. The volunteer must rate the level of discomfort by marking a straight vertical line on the horizontal line of a 100 mm rating scale. Higher values indicate greater soreness.

The fear of movement will be assessed with the Tampa Scale for Kinesiophobia. A questionnaire of 17 questions, with a maximum of 68 points. Scores > 37 points indicate high levels of kinesiophobia, and ˂ 37 points indicate low levels.

The catastrophization of pain will be assessed with a self-reported questionnaire designed to assess catastrophic thinking related to pain among adults. This "Pain Catastrophizing Scale" has 13 items, each describing a thought or feeling about pain. Each item is rated on a 5-point Likert scale from 0 to 4, with a maximal score of 52. Higher scores indicate high catastrophising.

The acceptance of chronic Pain will be assessed with a 20-item questionnaire, "Chronic Pain Acceptance Questionnaire for Fibromyalgia", scored with a 7-point Likert scale (0 = "never true" to 6 = "always true"). Higher scores indicate better adjustment and functioning.

The weight and body composition in percentage of muscle, fat and water will be measured with a bioimpedanciometer (InBody 770).