Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double–Blind Clinical Trial Study Protocol

Abstract

BackgroundDespite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP.ObjectiveThe objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees.MethodsA prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention.ResultsThis clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years.ConclusionsThis factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention.Trial RegistrationClinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf)

Motor Cortex Reorganization in Limb Amputation: A Systematic Review of TMS Motor Mapping Studies

“…There is a notion that changes in cortical mapping are related to the presence of acute and chronic pain. One of the ideas recently hypothesized is that pain can itself cause reorganization of the motor cortex (Pinto et al, 2016). The exact mechanisms by which these alterations can correlate with pain presence are far from being understood.…”

“…Thus, rather than focusing on correlation with the intensity of the pain, future studies should focus on using TMS measurements as neurophysiologic predictors for the identification of potential patients with increased risk in developing phantom pain. Likewise, TMS evaluation can also be used as a follow-up measurement that will allow determining if a specific treatment is leading to plastic changes (in plain words the disorganization is being reorganized) and if these changes can be dependent on the treatment being tested (Pinto et al, 2016).…”

Surface EEG-Transcranial Direct Current Stimulation (tDCS) Closed-Loop System

“…47–49 Therefore, one potential application is to use behavioral interventions such as visual illusion (mirror therapy is an example) to induce changes in motor cortex excitability and combine with tdcs to modulate pain-related circuits. 50 In such study, a detailed recording of motor cortex excitability could be used to trigger (and also stop) tDCS of primary motor cortex to reduce pain. In fact, unnecessary prolonged tDCS could lead to opposite effects.…”

A case report of a Phantom Limb Pain (PLP) patient treated with integrative Korean and Western medicine

“…The pain becomes chronic 10,11) . Approximately 59% of patients show a 5-10% reduction in pain intensity even 2 years after amputation 12) .…”