Searching for the optimal Transcranial Direct Current Stimulation ( TDCS ) target combined with peripheral electrical stimulation in chronic low back pain : a protocol for a randomized controlled trial

Backgroud: Low back pain (LBP) has been associated with severe impairments, primarily related to activities of daily living, functional ability and quality of life. A multimodal approach to pain management, such as transcranial direct current stimulation (tDCS) and peripheral electrical stimulation (PES), may improve outcomes in chronic LBP. However, the optimal cerebral target for stimulation still remains controversial. This pilot trial aims to investigate whether active stimulation could promote additional gains to the PES results in LBP patients. Our secondary objective is to investigate whether the stimulation of primary motor cortex and dorsolateral prefrontal cortex results in distinct clinical effects for the patients involved. Methods: Sixty patients with chronic low back pain will be randomized into one of three tDCS groups associated with PES: motor primary cortex, dorsolateral prefrontal cortex and sham stimulation. Each group will receive transcranial direct current stimulation at an intensity of 2 mA for 30 minutes daily for 10 consecutive days. Patients will be assessed with a Brief Pain Inventory (BPI), Roland Morris Disability Questionnaire (RMDQ), Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and electromyography at baseline, endpoint (after 10 sessions) and 1-month follow up. Discussion: This study will help to clarify the additive effects of tDCS combined with peripheral electrical stimulation on pain relief, muscle function and improvement in quality of life. Additionally, we will provide data to identify optimal targets for management of chronic low back pain.


Recruitment
The study will be conducted in a Public Neuromodulation Unit, which provides specialized assistance to patients with chronic pain (cLBP). Participants will be recruited from hospitals and clinics, as well as through social media and support groups. Written and informed consent will be obtained from all participants and those interested in participating will have their records reviewed and will be contacted for inclusion in the study, according to the eligibility criteria.

Randomization and Blinding
Participants will be randomly allocated via an online generator (www.random.org) in one of three groups (1:1:1): anodal tDCS of M1 + PES; anodal tDCS of DLPFC + PES; Sham of M1 + PES. This sequence will be performed blindly, independently, and remotely by a blind investigator who will have no contact with other research procedures, and randomization will be hidden until the group is allocated.
The hidden allocation process will be performed using sequential, numbered, opaque and sealed envelopes. The outcome assessors, trialists and participants will be blinded to the performed procedures.

Attrition and Adherence
Attrition will be considered under the following conditions: (a) two consecutive or three alternating absences during treatment; (b) the inability to complete the post-test and follow-up; and (c) the development of any disabling condition preventing the participant's participation in the study. Regarding adherence strategies, up to two non-consecutives absences can be compensated the following week. Flexible therapy hours will also be offered, and the relatives of the patients will be directly contacted by telephone to confirm the dates of evaluation, thereby reinforcing treatment adherence (Brunoni, et al., 2011). Additional measures to avoid dropouts will also be applied, including periodic assessments of treatment satisfaction, discussion of difficulties in continuing treatment (for example, logistics of the trips to the laboratory) and attempts to resolve and avoid possible problems that may affect adherence to and continued participation in the study. Research, Society andDevelopment, v. 9, n. 12, e38991211318, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i12.11318 and 4x4 cm sponges moistened with 0.9% saline solution. The anodic electrode will be placed on C3 to stimulate the left primary motor cortex and on F3 to stimulate the left dorsolateral cortex according to the international 10-20 EEG system (Homan, Herman & Purdy, 1987).
For sham stimulation, the anodic electrode will be positioned on the left primary motor cortex, but the current will be turned off automatically after 30 seconds. The reference electrode will be positioned in the supra orbital contralateral region for all groups.
To verify the chosen electrode configuration, we will perform a simulation of the current distribution and flow for the mentioned tDCS configuration (Figure 2)

PES
The participants will be positioned in ventral decubitus position and submitted to continuous application of PES for 30 minutes, using a strong but comfortable intensity adjusted according to the sensitivity of each volunteer. Four self-adhesive electrodes with dimensions of 5 x 5 cm will be placed at the height between the T12 and S1 vertebrae in order to cover the entire lumbar area. A 20Hz frequency and pulse duration of 330ms will be