Repetitive transcranial magnetic stimulation (rTMS) significantly reduced phantom limb pain in patients who had lost limbs to land mine explosions for up to 15 days, according to a study in the Journal of Pain (2016 ;17:911-918). Sixty-three percent of patients experienced a greater than 50% reduction in pain. No significant side effects were reported.
Fifty-four patients with phantom limb pain caused by land mine explosions were randomly assigned into the double-blind, placebo-controlled trial. They were treated with real or sham rTMS applied over the area corresponding to the motor cortex contralateral to the amputated leg for 20 minutes per day for 10 days. The investigators measured pain levels using a visual analog scale.
The impetus for the study was reports showing that invasive electrical stimulation of the motor cortex via electrodes surgically implanted in the cortex was effective for treatment of neuropathic pain, said corresponding author Ronald Garcia, MD, PhD, research fellow at Massachusetts General Hospital and Harvard Medical School, in Boston. rTMS, he said, provided a noninvasive alternative.
Seventy percent of patients in the active arm achieved at least a 30% reduction in pain scores, compared with 40% in the sham group. The level of pain reduction averaged 30% greater in the active arm than in the placebo group 15 days post-treatment. In fact, 63% of active-arm patients achieved a reduction of greater than 50%. There were no serious side effects, but some patients had headaches or drowsiness.
However, the benefits were no longer clinically relevant at 30 days post-treatment. “We still need to identify appropriate stimulation protocols—frequency and number of stimulation sessions—associated with a more long-lasting response,” Dr. Garcia said.
He noted that in other chronic pain disorders, daily stimulation for one week followed by weekly maintenance sessions for one month, and then every two weeks for two months, has shown long-lasting analgesia without any significant adverse events.
“This paper is one of many reports that have sought to use noninvasive brain stimulation to address phantom limb pain,” said Scott Frey, PhD, the Miller Family Chair in Cognitive Neuroscience in the Department of Psychological Sciences at the University of Missouri, in Columbia, who works extensively with amputees and nerve injury patients. “This work is distinguished by its use of a largely homogeneous sample and by the fact that treatment was continued for a full 10 days,” said Dr. Frey, who was not involved in the research.
Although the study was “double-blinded in the abstract,” Dr. Frey suggested that both patients and health care personnel delivering the treatments probably could discern which treatment was being delivered, which “may have affected outcomes.”
But Dr. Garcia said investigators evaluating the level of pain reduction lacked information about treatment allocation in the trial, and that at the trial’s end, patients’ ability to say correctly whether they had received rTMS or sham treatment was no better than chance.
Additionally, said Dr. Frey, follow-up treatments might be needed to make the pain relief longer-lasting, but “we do not have a lot of information about possible adverse neurological/behavioral effects from such extended epochs of rTMS. … I don’t think we should [assume] that the modest potential benefits demonstrated here outweigh potential risks at this stage.”
Phantom limb pain is highly prevalent among patients with traumatic amputations, with more than 70% of people experiencing persistent pain six months after limb loss, Dr. Garcia said. Additionally, it is associated with significant disability and reduced quality of life. Existing treatments don’t work well, and use of medications is limited by their side effects, he said.