Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial

Abstract

We evaluated the effects of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of phantom limb pain (PLP) in landmine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded placebo-controlled parallel group, single center trial. The intervention consisted in real or sham rTMS of M1 contralateral to the amputated leg. RTMS was given in series of 20 trains of 6s of duration (54 s inter-train, intensity 90% of Motor Threshold) at a stimulation rate of 10 Hz (1200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (Visual Analogue Scale scores) fifteen days after treatment when compared to sham stimulation (−53.38±53.12% vs −22.93±57.16%; mean between-group difference=30.44%, 95%CI 0.30, 60.58; p=0.03). This effect was not significant 30 days after treatment. In addition, 70.3% (19) of subjects attained a clinically significant pain reduction (>30%) in the active group compared to 40.7% (11) in the sham group fifteen days after treatment (p=0.03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induces significant clinical improvement in pain. Trial registry www.clinicaltrials.gov: Code Number: NCT01872481 Perspective High frequency rTMS on the contralateral primary motor cortex of traumatic amputees induces a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with phantom limb pain caused by landmine explosions.

Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review

“…Phantom limb pain (PLP) is a neuropathic syndrome described as pain felt in the patients' remaining perception of an amputated limb and is characterized by a stabbing, throbbing, burning, or cramping sensation (93). PLP can be severe, intractable, and debilitating and occurs in up to 80% of patients after limb amputation (91,124).…”

“…Our literature search revealed two RCTs (89,93) and five case studies (88,(90)(91)(92)94) that reported that the application of rTMS effectively reduced the pain associated with PLP. In 2011, Ahmed et al (89) applied 20-Hz rTMS to amputated patients with chronic PLP over the hand area of the M1 for 5 consecutive days.…”

“…As compared with 10 patients who received sham stimulation, 17 patients who received rTMS reported longlasting pain relief for up to 2 months, and serum β endorphin levels increased significantly after rTMS. In 2016, Malavera et al (93) conducted an RCT with 54 land mine victims and compared 10 sessions of 10-Hz rTMS over the M1 to sham stimulation (27 patients in each group). The VAS scores of patients in the rTMS group were significantly decreased as compared with those in the sham group (-5 for rTMS and−2 for sham) 15 days after the treatment, but the effect had dissipated by 30 days after treatment.…”

Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain: Probably Effective but Understudied

“…They found that high-frequency rTMS on the contralateral primary MC could reduce pain up to 15 days after treatment without any major sideeffects. Their study result introduces rTMS as a safe and effective therapy for PLP reduction (7). In another study, Ahmed et al found that rTMS can produces long lasting PLP relief.…”

Strategies for replacing non-invasive brain stimulation sessions: recommendations for designing neurostimulation clinical trials

“…Ambriz-Tutut et al (2016) removed a subject due to "poor compliance", however they do not explicitly describe their definition of adherence [30]. Malavera et al (2016) excluded participants that missed one or more day(s) of stimulation [31].…”