Pregabalin Acute Effects on Cortical Excitability, Psychophysical Parameters, and Serum Markers of Neuroplastic Processes in Fibromyalgia: a Placebo Controlled, Double Blinded, Randomized, Crossover Clinical Trial

A crossover, double-blinded randomized clinical trial is proposed. The investigators will recruit literate adult females aging 18 to 65 years old; fulfilling the diagnosis criteria for fibromyalgia according to the American College of Rheumatology 2010; with mean pain ≥6 in the verbal analog scale; who speak Brazilian Portuguese; and were able to perform the three visits. Female adult participants without chronic pain will also be recruited. Participants with severe psychiatric disorders that would limit consenting; neurologic deficits; decompensated systemic disease or chronic inflammatory disorders (Systemic Erythematous Lupus or Rheumatoid arthritis); contraindications for TMS; and those with previous use of Pregabalin will be excluded.

In the investigators' study, participants will be asked to visit the investigators' laboratory in three opportunities: one for a baseline assessment, and the other two to test the effects of either Pregabalin 150 mg PO or Placebo. All participants will eventually receive both, Pregabalin and Placebo. In each visit a brain hemodynamic, electrical, hormonal and clinical evaluation will be performed.

In the first visit, after explaining the research, solving doubts and signing the informed consent, participants will be randomized to an allocation sequence (either Pregabalin in the second or in the third visit). Then, a blood sample will be gathered and participants will be asked to fill some questionnaires to understand better their pain, and its impact on their quality of life (Fibromyalgia Impact Questionnaire), Anxiety (State/Trait Anxiety Inventory), Depressive symptoms (Beck Depression Inventory II), Catastrophizing thinking (Pain Catastrophizing Scale - PCS), Sleep (Pittsburgh Sleep Quality Index), and resiliency. Then, a fingertapping task will be performed while assessing hemodynamic changes using fNIRS. After that, heat perception will be tested using quantitative sensory testing (QST) and Conditioned Pain Modulation (CPM) with cold. Also, the pain pressure threshold (PPT) using a digital algometer will be evaluated. Finally, cortical excitability parameters (motor evoked potentials, intracortical facilitation and inhibition, and cortical silent period) will be determined using paired pulsed TMS.

In the second visit, according to the randomized allocation participants will receive either Pregabalin 150 mg PO or Placebo. Then, the M.I.N.I. International Neuropsychiatric Interview will be performed. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a new blood sample will be collected. In the third visit, a blood sample will be gathered, followed by administration of the corresponding intervention according to the randomized allocation. Then, the pain level, PCS, STAI and International Physical Activity Questionnaire (IPAQ) will be asked again. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a final blood sample will be collected. Participants' guess about blinding will be assessed after each intervention. All evaluators will remain blind to the allocation.