Additive effect of tDCS combined with Peripheral Electrical Stimulation to an exercise program in pain control in knee osteoarthritis: study protocol for a randomized controlled trial

Luz-Santos et al. Trials (2017) 18:609 DOI 10.1186/s13063-017-2332-6 STUDY PROTOCOL Open Access Additive effect of tDCS combined with Peripheral Electrical Stimulation to an exercise program in pain control in knee osteoarthritis: study protocol for a randomized controlled trial Cleber Luz-Santos1,2, Janine Ribeiro Camatti1,6,7, Alaí Barbosa Paixão1,2, Katia Nunes Sá1,3, Pedro Montoya4, Michael Lee5 and Abrahão Fontes Baptista1,2,6,7* Abstract Background: Knee 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. Methods: Patients 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. Discussion: The 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 registration: ID: RBR-9D7C7B. Registered on 29 February 2016. Keywords: Knee osteoarthritis, Pain, Exercise, Transcranial direct current stimulation * Correspondence: 1 Functional Electrostimulation Laboratory, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil 2 Graduate Program in Medicine and Health, Faculty of Medicine, Federal University of Bahia, Salvador, Brazil Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Luz-Santos et al. Trials (2017) 18:609 Background Osteoarthritis (OA) is a chronic degenerative disease, primarily affecting the articular cartilage and subchondral bone of a synovial joint [1]. Radiographic features of OA include degradation of the articular cartilage, subchondral sclerosis and osteophyte formation [2, 3]. OA primarily affects the large, weight-bearing joints such as the knee and hip [4, 5]. The hallmark symptom of OA is chronic joint pain, which contributes to functional limitation and is a major cause of reduced quality of life. OA is the leading cause of disability affecting up to 15% of the global population, that equates to approximately 630 million people worldwide [6]. In South America, the prevalence of arthritis and rheumatism has been reported to range between 23.8 and 56.0% [7]. In Brazil, direct OA data is not available but chronic knee pain affects approximately 11.2% of the population [8]. Knee OA affects around 10% of people over 55 years old, a quarter of whom are severely disabled [2]. Thus, knee OA poses a considerable economic burden to the community [9] due to indirect expenses incurred by patients, such as home adaptations, medications [10, 11], costs incurred for loss of employment and productivity [12]. A recent study in the United States revealed that lifetime direct medical costs of people with knee OA totaled US$129,600 [13]. Therefore, knee OA is considered a significant global public health problem, especially with an ageing population. The development of OA is multifactorial (Fig. 1) but some main risk factors have been identified, and these include obesity, female gender, and previous knee injury [14]. However, previous research also noted the influence of age, genetic susceptibility, trauma (acute or repetitive), muscle weakness, joint laxity, and abnormal mechanical forces, such as repetitive kneeling and squatting, as important risk factors [15]. Abnormal mechanical stresses can impede natural repair and remodeling processes of the articular cartilage [16, 17]. The source of abnormal mechanical stress is Page 2 of 11 diverse but has been associated with decreased postural control [18], muscle weakness and increased co-activation [19, 20], abnormal cumulative load [21, 22], joint instability [23], and the presence of abnormal tissue inside the joint (e.g., polymers of homogentisic acid oxidase in osteonecrosis) [16]. Conservative management, such as exercise therapy, designed to address issues like postural control and muscle dysfunction have limited success [24, 25]. Although the influence of OA on muscle strength is controversial, strengthening, stretching, and aerobic exercise are generally recommended [26]. A recent systematic review that pooled data from 44 trials concluded that land-based therapeutic exercises provide short-term pain relief (12 points/100) and improved physical function (10 points/ 100) for people with knee OA [27, 28]. After around 6 months, the benefits of exercise generally plateau, and pain often persist [27, 29]. The refractoriness to exercises needs to be addressed, and many factors may contribute. An alternative explanation for the (...truncated)