Cause of Phantom Limb Pain Still Elusive

As its name implies,
phantom limb pain is a shadowy entity that is difficult to
predict, understand and manage. Although postamputation pain has been
recognized by patients and physicians for centuries, Silas Weir Mitchell, MD, a
Civil War battlefield surgeon who later became a neurologist, has been credited
with coining the term phantom limb pain and providing an in-depth description
of the phenomenon.

Although phantom limb pain was long characterized as primarily a
psychiatric illness, this is no longer the case. However, the exact mechanism
of phantom limb pain remains a mystery. Many theories regarding the
pathophysiology of phantom limb pain abound, and treatment options are almost
as varied.

Image: US Defense Department photo, Donna Miles


Prevalence and risk

The number of amputees who will experience phantom limb pain at some
point after undergoing an amputation has been estimated to be as high as 90%. A
number of predictors or risk factors for phantom limb pain have emerged from
research studies, Bishnu Subedi, MD, a psychiatry resident from the department
of neurology and psychiatry, Saint Louis University School of Medicine, told
O&P Business News.

Subedi noted that phantom limb pain occurs more often in females than in
males. The site of the amputation also is a factor; patients who undergo upper
extremity amputation have a greater chance of developing phantom limb pain than
patients who undergo lower extremity amputation.


In addition, patients who have pain before amputation have a greater
chance of experiencing phantom limb pain, and stump or residual pain is another
factor. Finally, the time after amputation also plays a role. The risk is
greater during the first month after amputation and then again at 1 year after
amputation, and then gradually decreases with time.

For patients who experience phantom limb pain, the symptoms and
intensity can vary substantially, with some patients experiencing pain that is
severe and debilitating. Phantom limb pain also can be permanent for some

“There were people in my study who had phantom pain for 59 years.
That is lifelong,” Beth Darnall, PhD, assistant professor of
anesthesiology and perioperative medicine, Oregon Heath and Science University,
told O&P Business News. “It is not necessarily permanent
for everybody, but it does become chronic for many people, and once it becomes
chronic, people may have it for years, decades or their entire life. That is a
really significant burden on quality of life.”

Mismatch in signaling

One of the theories for phantom pain is that there is a mismatch in
signaling in the brain. When a limb is amputated, the neurons in the brain that
control movements are still present, and it is thought that the neurons may
start sending out new conflicting signals, which the brain then interprets as
phantom pain and the phantom limb resurrected, Jack Tsao, MD, DPhil, director
of Traumatic Brain Injury Programs for the U.S. Navy Bureau of Medicine and
Surgery and associate professor of neurology and neuroscience, Uniformed
Services University of the Health Sciences, said.

  Bishnu Subedi
  Bishnu Subedi

“The theory is that with typical movements, for example, if you are
reaching out for your coffee cup, vision guides your hand in an overriding
component of driving movements and goals. What happens is that if you were
blind, it would just be proprioception because as your hand is moving through
space, it is giving the brain feedback as to where it is in space,” Tsao
told O&P Business News. “That is proprioception, and so
with all movements, it is a combination of vision and proprioception, with
vision overriding proprioception.”

A second explanation may be something that Tsao described as
proprioceptive memory. He noted that amputees often describe the exact position
of their phantom limb and the sensations they experience in the limb.

“As an example, I had one Marine who lost his hand in a gun fight,
and he said his phantom pain was that his hand was holding the rifle. His index
finger was pulling the trigger and he could not release it. He also said his
hand felt like the muscles were cramping up, so it was a completely vivid
description of not only the other muscles of the hand moving in certain
positions but also the finger not being able to release,” Tsao said.
“So we think that there is some other aspect of memory for limb position
or something that is also called in by the brain as it experiences the phantom


Treatment options

Management of phantom limb pain often requires a trial-and-error
approach to determine what treatment will work best for patients. Consequently,
the management of phantom limb therapy must be customized to individual
patients rather than following a specific protocol. Subedi advocates using a
multidisciplinary team approach, with the team composed of psychiatrists,
primary care doctors, orthopedists, neurologists and physical therapists as
well as any additional support staff who assist patients in their activities of
daily living.

Pharmacological treatment also should be approached on a case-by-case
basis. As patients go through amputation and its aftermath, they may experience
psychiatric problems. Subedi noted that medications such as tricyclic
antidepressants or anticonvulsants used to treat psychiatric conditions have
been found to be useful in the treatment of phantom limb pain. Pain medications
such as tramadol to control the pain and morphine in the acute painful
conditions also have been used.

“There is no hard and fast answer, no protocol on which medications
to use first and then which medications to go to second,” Subedi said.
“Of course, the basics, such as an infection or inflammation, must be
taken care of first before giving a thought to the choice of other

Nonpharmacological therapies also have been found to be effective.
However, Subedi noted that the reports regarding many of these treatments have
been case-based rather than randomized clinical trials.

“Transcutaneous nerve stimulation, which now is pretty common, is
relatively user friendly therapy. Many have used it as treatment. It is
relatively simple and patients have full control,” Subedi said. “The
other therapies are temperature biofeedback, massage, ultrasound local area and
guided behavioral therapy for pain management.”

Surgical intervention should be considered the second line of treatment.
Procedures such as stump revision or nerve blocks may help alleviate phantom
limb pain.

Mirror therapy

One noninvasive therapy that has been growing in use for the treatment
of phantom limb pain is
mirror therapy. First described in the mid-1990s by Vilayanur
S. Ramachandran, PhD, mirror therapy initially was a novel and experimental
approach that was not widely used clinically. However, by 2007, more reports
began appearing in the literature on the success of mirror therapy as a
treatment for phantom limb pain.

“That is the time when mirror therapy really seemed to start coming
more and more into the consciousness of pain professionals. It started being
described more as a simpler technique,” Darnall said.

Essentially, there are three components to mirror therapy, Tsao said. As
patients move their intact limb and look in the mirror, the visual input is
seeing the reflection of the hand moving, and patients feel they are moving the
phantom limb around.

Tsao first became interested in mirror therapy around 2005. As a
neurologist with the US Navy, he found that approximately 85% to 90% of
amputees in the military experienced phantom limb pain at some point in time
after undergoing amputation. He remembered reading Ramachandran’s original
case series study from the mid-1990s and wondered why mirror therapy might work
in treating phantom limb pain. After receiving funding, Tsao set up a small
study to examine whether mirror therapy would actually work to treat phantom
limb pain, and if so, which component of mirror therapy modulated the pain

The ensuing study randomized lower extremity amputees into three groups.
In the first group, participants were asked to move their foot, look in the
mirror and move their phantom foot. In the second group, the mirror was covered
with a sheet and participants were asked to move their intact foot and their
phantom foot around in similar movements. In the third group, participants were
instructed to close their eyes and imagine moving their foot around, the
amputated one or phantom. Therapy lasted for 15 minutes 5 days a week for 4

“What we found was that the mirror group within a week and
continuing onwards had decreased pain. All of the patients had some improvement
to varying degrees. The covered mirror group did not seem to change,” Tsao
said. “At the end of that period, we switched over those who wanted to
continue from the covered mirror and the mental visualization groups to the
mirror group. So the covered mirror group had no change in pain relatively
speaking over the 4 weeks and then when they changed over, they all improved.
The mental visualization group, on the other hand, some of them worsened and
then when people switched over, they improved as well.”

Tsao noted that the participants in the mental visualization group were
actually making a dissociation between the signals. The vision and
proprioception mismatch became greater by increasing proprioceptive feedback
without giving any visual input, which could explain why pain worsened.

“Not everyone responds equally to mirror therapy,” Tsao said.
“Some people take longer, and there are certain people who do not seem to
respond at all, so it is not 100% perfect, unfortunately.”

The next step in Tsao’s research is to examine why phantom limb
pain typically starts and disappears over a certain number of months. He
expects to launch a genetic study soon to address this.

Cause of Phantom Pain


“We think that some people never have phantom limb pain, so there
must be something protective going on,” he said. “It may be a gene
that is modulating and the effect is only seen whenever you have an

Guided vs. self-therapy

In addition to being a noninvasive, low-cost and relatively simple
treatment, mirror therapy can be guided by a therapist or by patients

“At first there was a lot of mystique around mirror therapy and
while people were very interested in it, there was this assumption that you had
to go see a specialist or you needed to work with someone who knew about mirror
therapy because people were perplexed about the mechanism. How does this work,
and why does it work? Nobody was really sure quite how to do it,” Darnall
said. “I think it conveyed this notion that it was a little more
complicated and structured than perhaps it really is, and my clinical
experience was that mirror therapy was quite simple.”

Based on her initial success with a patient who successfully
self-treated his phantom limb pain, Darnall launched a small study to determine
whether patients would be able to self-treat their phantom limb pain using
mirror therapy with only basic instruction and no structured guidance from a

“There are two aspects to this notion of needing therapist
guidance. One is does the therapist provide knowledge and true mechanical
guidance that is important for the patient,” Darnall said. “That is
number one, but number two, just showing up and working with the therapist
means you are actually going to do something. It holds the patient

The primary goal of her study was to determine whether patients would
perform mirror therapy on their own if they did not meet a therapist every week
outside of the home. Darnall discovered that 31 of the 40 patients in her study
were motivated and were able to self-treat. Her findings also indicated that
self-treatment mirror therapy was very effective for a subset of people.

“Like any pain treatment, it is not 100% effective for everybody.
There were 9 people in the study who achieved what we would call either a
moderate or a substantial improvement in their pain, meaning that their
improvement in their phantom pain was in the range of 30% to 100% resolution.
That is very significant in the pain world,” Darnall said. “In other
words, about a third of the people who initiated mirror therapy achieved a
moderate or significant reduction in their phantom pain.”

The study also revealed that for fully self-delivered mirror therapy,
education was a significant predictor for treatment response. Patients who had
higher levels of education were more likely to respond to mirror therapy and
experienced greater reductions in their phantom limb pain. However, Darnall
cautioned that this finding does not necessarily mean that mirror therapy works
better for people who are more educated.

“What I showed in my study was that people who are better educated
are more likely to have a better result with self-treatment, so it could be
that the people who were less educated just need that weekly follow-up with the
therapist,” Darnall said. “Maybe they are just not doing the
treatment every week or they are not engaged at the level that would be
required to experience that positive therapeutic result. So, maybe these are
the people who need ongoing structure, ongoing guidance.”

Darnall described mirror therapy as currently being the most researched
treatment for phantom pain, “primarily because it is effective. For those
people for whom mirror therapy works, it is more effective than any other
treatment.” — by Mary L. Jerrell, ELS

For more information:

  • Subedi B. Phantom limb pain: Mechanisms and treatment
    approaches. Pain Research and Treatment. 2011; article ID: 864605;

  • Chan BL. Mirror therapy for phantom limb pain. N Engl J
    . 2007; 357(21):2206- 2207.

  • Darnall BD. Self-delivered home-based mirror therapy for lower
    limb phantom pain. Am J Phys Med Rehabil. 2009;

Disclosure: Darnall receives a portion
of the proceeds of “Do it Yourself Mirror Therapy” © 2010, a
commercial DVD. Subedi and Tsao reported no relevant financial disclosures.

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