Brain Stimulation Effective for Phantom Limb Pain

Patients with traumatic amputations resulting from land mine explosions show significant improvement in phantom limb pain after repetitive treatments of high-frequency transcranial stimulation (rTMS), new research shows.

“Our study is the first randomized clinical trial demonstrating significant effects of transcranial magnetic stimulation in patients with phantom limb pain caused by traumatic amputations,” coauthor Ronald G. Garcia, MD, PhD, from Massachusetts General Hospital and Harvard Medical School, Boston, tells Medscape Medical News.

“This therapy looks particularly promising because 70% of subjects presented a significant pain reduction and 63% attained a substantial clinical benefit after treatment without any major side effect reported.”

The study, published in the August issue of the Journal of Pain, involved 54 patients, all of whom had traumatic lower limb amputation as a result of land mine explosions, recruited from the rehabilitation department of the Regional Military Hospital and other organizations in Bucaramanga, Colombia.

Fifty patients were male and four were female; the mean age was 33.9 years. All patients had symptoms of phantom limb pain, including shooting, stabbing, boring, squeezing, throbbing, burning or paresthesia, or any other pain in a limb that had been amputated.

After a week of establishment of baseline measures of pain, depression, and anxiety, the patients were randomly assigned 1:1 to receive real rTMS directed to the primary motor cortex, contralateral to the amputated leg, or a sham coil. The rTMS was given in series of 20 trains of 6-second duration at a stimulation rate of 10 Hz (1200 pulses), for 20 minutes per day, over 10 days.

Pain reduction, assessed according to visual analogue scale scores, was significantly greater in the rTMS group 15 days after the treatment compared with the sham group (–53.38% ± 53.12% vs –22.93% ± 57.16%; mean between-group difference, 30.44%; P = .03).

Differences between the two groups were not significant, however, 30 days after treatment.

Nineteen patients (70.3%) in the rTMS group achieved a clinically significant pain reduction of greater than 30% compared with 11 (40.7%) in the sham group 15 days after treatment (P = .03).

The authors noted that the improvement represents a number needed to treat of 4, suggesting that 1 patient in every 4 patients treated with the approach could be expected to achieve at least a 30% reduction in pain.

“This effect size is similar to tricyclic antidepressants for the treatment of central pain,” the authors noted.

Only three other trials have looked at rTMS for phantom limb pain, including two small pilot studies and one randomized controlled trial of 27 patients showing an analgesic effect lasting up to 2 months in 39% of patients treated over five consecutive sessions.

A recent meta-analysis concluded, however, that the latter study had deficient randomization and was therefore at a high risk of bias.

Daily applications of rTMS over the primary motor cortex have been shown to offer benefit in various other neuropathic pain syndromes, including post-stroke pain and spinal cord injury pain, the authors note.

With as many as 87% of all amputees experiencing phantom limb pain, and few treatments offering any significant efficacy, the new findings are encouraging, Dr Garcia said.

“These results point out to the fact that the therapy has the potential to be effective several weeks after treatment, but we still need to identify appropriate stimulation protocols, such as frequency and number of stimulation sessions, associated with a more long-lasting response.”

Strategies that could potentially improve response could include periodic maintenance sessions after an initial induction treatment, and the selection of patients most likely to benefit, Dr Garcia said.

“For instance, in a recent subgroup analysis, we found that patients with less than 5 years since diagnosis got a longer-lasting effect compared with those with a more chronic disease course,” he said.

“Future studies will need to include larger sample sizes that allow identifying which particular clinical characteristics from this population are associated with a greater response to this technique.”

Important Insights

Jack Tsao, MD, DPhil, a professor of neurology at the University of Tennessee Health Science Center in Memphis, said the study contributes important insights into the potential value of rTMS for phantom limb pain treatment.

“This is a well-designed, randomized clinical trial with a population with phantom pain which was uniform in mechanism of injury — landmine,” he told Medscape Medical News.

“It extends and confirms previous research showing that rTMS shows promise as a treatment for phantom limb pain, delineating the treatment Hz and defining duration of therapy to achieve a response,” he said.

Dr Tsao, who, as reported by Medscape Medical News, has published studies looking at the benefits of mirror therapy with phantom pain, said that with no significant response seen in patients at 30 days, information on the details of those who did respond would be helpful.

“It would have been of interest to see how soon a response to rTMS was seen,” he said, adding that “it is possible that pain at onset may affect length of time needed for rTMS treatment.”

The degree of pain reported in the study is also notable, Dr Tsao says.

“Pain levels were still around 3 out of 10 in the responder group, which is mild pain,” he said. “It would have been interesting to see how many had no pain at 15 and 30 days.”

Dr Tsao adds that, with medication showing poor efficacy in treating phantom pain and the potential for long-term pain from the syndrome, nonpharmacologic treatments should continue to be pursued.

“Contrary to previously published reports which suggested that phantom pain eventually resolves spontaneously, we have unpublished data from a genetics study of phantom pain that we are conducting, which suggests that many people have chronic phantom pain lasting years to over a decade,” he says.

“Of the nonpharmacological treatments, mirror therapy appears the most promising, although rTMS certainly also has promise.”

The study was partially supported by a grant from the Colombian Science and Technology Institute (COLCIENCIAS).