BackgroundKnee osteoarthritis (OA) has been linked to maladaptive plasticity in the brain, which may contribute to chronic pain. Neuromodulatory approaches, such as Transcranial Direct Current Stimulation (tDCS) and Peripheral Electrical Stimulation (PES), have been used therapeutically to counteract brain maladaptive plasticity. However, it is currently unclear whether these neuromodulatory techniques enhance the benefits of exercise when administered together. Therefore, this protocol aims to investigate whether the addition of tDCS combined or not with PES enhances the effects of a land-based strengthening exercise program in patients with knee OA.MethodsPatients with knee OA (n = 80) will undertake a structured exercise program for five consecutive days. In addition, they will be randomized into four subgroups receiving either active anodal tDCS and sham PES (group 1; n = 20), sham tDCS and active PES (group 2, n = 20), sham tDCS and PES (group 3, n = 20), or active tDCS and PES (group 4, n = 20) for 20 min/day for five consecutive days just prior to commencement of the exercise program. The primary outcomes will be subjective pain intensity (VAS) and related function (WOMAC). Secondary outcomes will include quality of life (SF-36), anxiety and depression symptoms (HAD), self-perception of improvement, pressure pain thresholds over the knee, quadriceps strength, and quadriceps electromyographic activity during maximum knee extension voluntary contraction. We will also investigate cortical excitability using transcranial magnetic stimulation. Outcome measures will be assessed at baseline, 1 month after, before any intervention, after 5 days of intervention, and at 1 month post exercise intervention.DiscussionThe motor cortex becomes less responsive in knee OA because of poorly adapted plastic changes, which can impede exercise therapy benefits. Adding tDCS and/or PES may help to counteract those maladaptive plastic changes and improve the benefits of exercises, and the combination of both neuromodulatory techniques must have a higher magnitude of effect. Trial registration: Brazilian Registry on Clinical Trials (ReBEC) – Effects of electrical stimulation over the skull and tight together with exercises for knee OA; protocol number RBR-9D7C7B.Trial registrationID: RBR-9D7C7B. Registered on 29 February 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2332-6) contains supplementary material, which is available to authorized users.