Current Treatments for Phantom Limb Pain
Over the past few years, military conflicts in Iraq and Afghanistan have resulted in a dramatic increase in the number of service members returning home with single- and multiple-limb amputations. For many of these individuals, pain from their injuries does not cease following amputation; many suffer from phantom limb pain (PLP), or pain that is perceived in an area of the body that no longer exists.
There are numerous theories behind the mechanisms of PLP and many treatment options. At the forefront of this research is CDR Jack Tsao, MD, DPhil, Director of Traumatic Brain Injury Programs for the US Navy Bureau of Medicine and Surgery in Washington, DC, and Associate Professor of Neurology and Neuroscience at the Uniformed Services University of the Health Sciences in Bethesda, MD. Dr. Tsao and his colleagues at Walter Reed Army Medical Center recently published a review article describing the various theories and therapies associated with PLP.1 Practical Pain Management spoke with Dr. Tsao to gain additional insight into recent developments regarding research in PLP.
Pathophysiology of PLP
Phantom limb pain can occur in many regions of the body, but limbs are the most common sites. PLP is actually one of three phenomena associated with what have been termed “phantom sensations” by Weinstein.2 He proposed that PLP fell under the category of “exteroceptive perceptions,” which include sensations such as touch, pressure, temperature, and itch. Naturally, PLP is of stronger intensity than phantom sensations. There are also kinetic sensations, which are the perceptions of movement, and kinesthetic components, which describe size, shape, and position of the missing limb. Attempts also have been made to characterize PLP,3,4 but the pathophysiology and etiology are unclear.
Several theories have been proposed to describe the origins of PLP, including cortical reorganization, body schema, and neuromatrix theory (see Weeks et al for a review).1 Dr. Tsao’s theory takes on a “multifactorial approach,” incorporating “proprioceptive memory” and Ramachandran and Hirstein’s model.5 Their model describes five sources involved in PLP: 1) residual limb neuromas, 2) remapping, 3) monitoring of corollary discharge from motor commands to the limb, 4) a primordial, internal “body” image, and 5) vivid somatic memories of painful sensations or posture of the original limb being “carried” over into the phantom. Proprioceptive memory refers to memory of specific limb positions.
Dr. Tsao and his colleagues proposed that proprioceptive memories remain in an individual even after a limb has been amputated.1 The brain mechanisms that sense proprioception remain intact, as do memories of limb position, and may be reactivated, thus giving rise to the phantom; the realization that a limb is missing arises then through the visual system, a relevant point for the upcoming discussion on treatment options.
Triggers of Pain
With regard to triggers, PLP “appears in our patients to be most often seen at the end of the day,” explained Dr. Tsao. Individuals are typically busy with activities during the day, so the experience of PLP is more pronounced when they are sitting
quietly at home at night. “Whether it is a nocturnal phenomenon or related to a lack of distractions is unclear,” Dr. Tsao noted. Individual experiences range greatly, especially among patients at Walter Reed. According to Dr. Tsao’s article,1 there are variations in onset, duration, description, and location of phantoms sensations and PLP. Some patients feel volitional control over their phantom, and some feel that the limb is fixed in a specific position. The authors described a particular patient who felt he was pulling the trigger on his rifle but unable to move his hand to a different position. With the range of unique individual experiences, finding a single effective treatment option presents a significant challenge to PLP researchers.
As with the experience of PLP, treatment options and success can vary. Most pharmacologic therapies have not met with success. Mixed results have been observed with memantine (Namenda), an oral N-methyl-daspartate (NMDA) receptor antagonist, but a review study suggests that memantine may be effective as a supplement for PLP in recent amputees but less effective for established chronic neuropathic pain.6 Other drugs have not been tested in controlled trials, so it is difficult to recommend any one treatment, noted Dr. Tsao.
Transcutaneous electrical nerve stimulation (TENS) is a promising nonpharmacologic treatment that involves brief, intense stimulations at trigger points or along the peripheral nerve of the residual limb. The average reduction in PLP with TENS was 66%, which was significantly more than with placebo.7 Deep brain stimulation, epidural spinal cord stimulation, anesthetic and surgical neuroablation, psychological interventions, and acupuncture have shown inconsistent results, either in short- or long-term relief of PLP.1
Thus far, mirror therapy has shown the most promise with regard to treating PLP. In this treatment, patients view the reflection of their intact limb moving in a mirror placed parasagitally between the arms or legs. Patients simultaneously move the phantom limb in a manner similar to what they are observing. As a neurologist in the US Navy, Dr. Tsao became interested in mirror therapy after observing the increase in the number of amputees from Iraq during 2004-2005. At about that time, Congress had appropriated funds for research on medical conditions affecting amputees. Dr. Tsao decided to approach the head of the rehabilitation department to discuss conducting a controlled trial to investigate the use of mirror therapy to treat PLP, because up to that time there had been no controlled trials to determine its efficacy.
Dr. Tsao and his colleagues decided that the best way to evaluate the efficacy of mirror therapy was to break it into three separate components: full mirror, covered mirror (to block reflection of the intact limb), or mental visualization of the phantom limb moving.8 Lower-limb amputees were randomized to one of these three treatments and received therapy for 15 minutes per weekday for 4 weeks. Participants viewed the virtual image in the mirror and repeated movements (eg, toe flexion and extension, rotation about the ankle, foot flexion) with their phantom limb. Pain scores were measured using a 100-mm visual analogue scale (VAS). After 4 weeks of treatment, 100% of patients in the mirror therapy group reported a decrease in pain compared with 17% in the covered mirror group, and 33% in the mental visualization group. Changes in scores on the VAS were significant: P=0.04 for full mirror versus covered mirror, and P=0.002 for full mirror versus mental visualization.