Neuromodulatory effects of Transcranial Pulsed Current Stimulation (tPCS) in Fibromyalgia: protocol for a double-blinded, sham-controlled, randomized clinical trial

Abstract

Fibromyalgia (FM) is a functional syndrome characterized by musculoskeletal, diffuse and persistent (> 3 months) chronic pain, that is also characterized by sleep disturbances, fatigue, humor changes and cognitive and psychological changes. Transcranial Pulsed Current Stimulation (tPCS) is a new Transcranial Electrical Stimulation (tES) that has been studied as a treatment option for chronic pain and neurological conditions . Studies have shown that tPCS is capable of pain and cognitive modulation; however, there are not enough studies with evidence of its efficacy.Therefore, the primary aim of this study is to evaluate the effects of tPCS in pain, evaluated through Visual Analogue Scale (VAS) in FM patients; besides that, it is aimed to evaluate the effects of tPCS on quality of life, cognitive impairments, pain pressure threshold, descending inhibitory system of pain, and serum levels of Brain Derived Neurotrophic Factor (BDNF) and S100 Calcium-Binding Protein B (S100B). A randomized, double-blinded, controlled with sham clinical trial will be conducted with 70 (Critical f: 2.003; ES: 0.76; alpha: 0.05; power: 0.80) women with Fibromyalgia, from 30 to 65 years with pain on the Visual Analogue Scale (VAS) higher than 6 in the last 3 months. All patients will read and sign an Informed Consent Form (ICF). Each patient will be randomized to either 1+4 sessions of tPCS (2mA,(20)(21)(22)(23)(24)(25) or Sham. Patients will complete the following questionnaires/tests: Visual Analogue Scale (VAS), Pittsburgh Sleep Quality Index (PSQI), Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), Profile of Chronic Pain (PCP), Conditioned Pain Modulation Task (CPM-T), Pain Pressure Threshold Task (PPT-T), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and blood collection for serum levels of BDNF and S100B. For the main outcome, comparison between variables during time will be made through linear regression, with an adjustment for baseline levels and possible confounders.

Transcranial pulsed current stimulation: A scoping review of the current literature on scope, nature, underlying mechanisms, and gaps

“…These studies demonstrated the significant positive effect of tPCS on a number of clinical conditions, including consciousness after brain injury (Barra et al., 2022), spasticity and movement disorders in patients with spinal cord injury (SCI) (Iddings et al., 2019, 2021; Liu et al., 2021), pain and cognition in fibromyalgia (Castro et al., 2021), cognitive dysfunction in schizophrenia (Singh et al., 2019), spastic cerebral palsy (SCP) (Thibaut, Russo, Morales‐Quezada, et al., 2017), and balance and movement in Parkinson's disease (Alon et al., 2012).…”

“…Since women's menstrual cycle may potentially affect the size of CSE induced by tPCS, some studies have exclusively recruited male participants 21–25 years old (Saito et al., 2019, 2022) or college athletes (Shen et al., 2022; Wu et al., 2022a, 2022b). In studies with patient populations, the sample sizes ranged from 6 to 70 participants between the ages of 2 and 85 (Alon et al., 2011; Barra et al., 2022; Castro et al., 2021; Iddings et al., 2019, 2021; Liu et al., 2021; Singh et al., 2019; Thibaut, Russo, Hurtado‐Puerto, et al., 2017). All these studies recruited both male and female participants, except one, which only recruited females with fibromyalgia (Castro et al., 2021).…”

“…The design, participants, tPCS stimulation protocol, and the study aim(s) are provided. Human studies on clinical conditions (2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022)(2023) These studies demonstrated the significant positive effect of tPCS on a number of clinical conditions, including consciousness after brain injury (Barra et al, 2022), spasticity and movement disorders in patients with spinal cord injury (SCI) (Iddings et al, 2019(Iddings et al, , 2021Liu et al, 2021), pain and cognition in fibromyalgia (Castro et al, 2021), cognitive dysfunction in schizophrenia (Singh et al, 2019), spastic cerebral palsy (SCP) , and balance and movement in Parkinson's disease (Alon et al, 2012).…”

“…Methodologically, except for four studies (Luu et al, 2016;Ma et al, 2019;Saito et al, 2019;Singh et al, 2019) that were not mentioned, all other studies employed randomized designs with either single-blinded Jaberzadeh et al, 2014Jaberzadeh et al, , 2015Mansouri et al, 2019;Paneri et al, 2016) or double-blinded (Barra et al, 2022;Liu et al, 2021;Morales-Quezada et al, 2014 Saavedra et al, 2014;Shen et al, 2022;Vasquez et al, 2016Vasquez et al, , 2017Wu et al, 2022aWu et al, , 2022b. Even though all included studies used sham stimulation as a control, four studies had control groups in which no intervention was administered (Barra et al, 2022;Castro et al, 2021;Iddings et al, 2021), and two studies did not refer to any control groups at all Vasquez et al, 2017). The cross-over design was employed in 13 studies, although two reported using parallel designs (Castro et al, 2021;.…”

“…The included studies examined different types of tPCS based on the applied waveforms and polarity. Eight studies indicated the effects of biphasic tPCS on cognitive-physical behaviors (Castro et al, 2021; and cortical coherence (Morales-Quezada, ; however, a study indicated no effect on learning or attention (Morales-Quezada et al, 2016). Some studies delivered by the a-tPCS reported significant modulation of CSE Jaberzadeh et al, 2014Jaberzadeh et al, , 2015.…”