A Closer Look At Evolving Treatments For Phantom Limb Pain

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A Primer On The Early Research Into Phantom Limb Pain

Ambroise Paré was a 16th-century French barber, a surgeon who served in the military. Paré documented the pain experienced by amputees who perceived sensation in the “phantom” amputated limb.51 Paré believed that phantom pains occur in the brain and not in the remnants of the limbs.

In 1872, American neurologist S. Weir Mitchell, MD, described a bizarre symptom complex resulting from wounds to peripheral nerves in his book, Injuries of Nerves and Their Consequences. Mitchell saw a large number of patients who had been wounded in the Civil War and suffered from a chronic affliction he called causalgia and coined the term “phantom limb pain,” recording an incidence as high as 90 percent.8,52 The common treatment for causalgia associated with peripheral nerve injury was amputation.

In 1937, Leriche wrote his classic work La Chirurgie de la Douleur, in which he detailed his work on causalgia and phantom limbs.53,54 He acknowledged Mitchell's contribution and looked for ways to solve the problem of pain. Leriche's opportunity to study phantom limb pain came during World War I when he saw many soldiers with peripheral nerve damage.54 He observed vasomotor changes, which suggested to him an abnormality of vascular stimulation. In 1916, he attempted to alleviate the pain through periarterial sympathectomy.54 Leriche also saw patients with painful stumps and phantom limb pain.

W.K. Livingston, MD, had learned at Harvard that pain was a specific response to an unpleasant stimulus, a warning of tissue damage. One of the problems that puzzled him early in his career was visceral pain. Patients might experience no apparent pain from tissue damage to certain internal organs but would report "referred pain" in another part of the body.54 He studied other pain phenomena, such as causalgia and phantom limb pain, which presented similar enigmas.54 During World War II, Livingston was assigned to the Oakland Naval Hospital, where he assumed responsibility for patients with peripheral nerve injury and other difficult pain problems, including causalgia cases.54 Livingston used periarterial sympathectomies, ganglionectomies and novocaine blocks to treat his patients, but he recorded several cases in which the relief was only temporary and the pain returned.54

Author(s): 
Robert G. Smith, DPM, MSc, RPh, C.Ped

   Memantine, which is commonly used to treat Alzheimer’s disease, produces an analgesic effect that may be beneficial in the treatment of phantom limb pain. Several case reports involving patients with severe phantom limb pain that was refractory to anticonvulsants, opioids and antidepressants demonstrated improved pain management with the use of memantine. One study using 20 to 45 mg per day in divided doses showed significant improvement in pain, resulting in a reduced dependence on opioids.43 However, other studies using doses of 20 to 30 mg per day were unsuccessful in proving the effectiveness of memantine versus placebo.44,45 Although memantine demonstrated promising results in several case studies, there is insufficient substantiating evidence to support its wide use in clinical practice.

   Other pharmacologic therapies. In one study surveying patient self-reported treatments, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) combined with opioids reportedly lessened pain intensity.46 The analgesic mechanism of acetaminophen is not clear but serotonergic and multiple other central nervous system pathways are likely to be involved.8 Other agents, such as propranolol (Inderal, Pfizer) and nifedipine (Procardia, Pfizer) have been effective in treating burning and cramping associated with phantom limb pain.8,47 Calcitonin may reduce the intensity and frequency of pain. However, a more recent randomized, placebo controlled trial showed that calcitonin alone was ineffective against phantom limb pain.8,9,48

Should You Consider Alternative Therapies?

Various non-pharmacologic options exist for managing phantom limb pain. These include transcutaneous electrical nerve stimulation, mirror therapy and surgical intervention.8,9,49 Of these treatments, mirror therapy is the most effective. One would place a mirror parasagittally between the patient’s lower limbs so there is a reflection of the intact limb. The reflection serves as a virtual representation of the missing limb.

   In one study, patients performed movements with their amputated limb while observing the movement of the intact limb in the mirror.49 This occurred for 15 minutes per day for four weeks. The mirror group reported a reduction in pain intensity and fewer episodes of breakthrough pain. The theory is that mirror therapy may help resolve the visual-proprioceptive dissociation associated with phantom limb pain.50

In Conclusion

Phantom limb pain is a relatively common and disabling entity. It is estimated that by 2050, there will be 3.6 million amputees in the U.S.1 Therefore, it has become increasingly important to understand and manage phantom limb pain properly. The management and treatment of neuropathic pain and phantom limb pain is complex since efficacy is mostly subjective. No single treatment is universally effective for phantom limb pain. One should tailor pharmacologic treatment to the patient and consider all concomitant disease states and medications.

   Dr. Smith is in private practice at Shoe String Podiatry in Ormond Beach, Fla. He is currently deployed.

References

1. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, et al. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008; 89(3):422-429.

2. Black LM, Persons RK, Jamieson B. What is the best way to manage phantom limb pain? J Fam Pract. 2009; 58(3):155-158.

3. Nikolajsen L, Jensen TS. Phantom limb pain. Br J Anaesth. 2001; 87(1):107-116.

4. U.S. OIF/OEF casualty statistics Department of Defense Statistics. Available at http://www.defenselink.mil/news/casualty.pdf . Accessed September 2013.

5. Tintle SM, Forsberg JA, Keeling JJ, et al. Lower extremity combat-related amputations. J Surgical Orthopaedics Advances. 2010; 19(1):35-43.

6. Clark RL, Bowling FL, Jepson F et al. Phantom limb pain after amputation in diabetic patients does not differ from that after amputation in nondiabetic patients. Pain 2013; 154(5):729-32.

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Bob Smithsays: October 5, 2013 at 10:59 pm

My deep gratitude to Podiatry Today and its staff for publishing this manuscript while I am away.

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DrDpmsays: October 30, 2013 at 1:13 pm

This is an excellent article on the topic of peripheral neuropathy! Phantom limb pain syndrome and residual limb pain syndrome are both variant examples of peripheral neuropathy in the distal lower extremities.

I disagree with this article that stated that people with peripheral neuropathy cannot feel the pain sensations from phantom or residual pain syndromes. Let me elaborate. There are two types of pain: nociceptive pain and neuropathic pain. A patient with diabetic neuropathy and residual pain syndrome (from an amputated toe) will not feel nociceptive pain but will feel neuropathic pain emanating from that amputated toe. Although the patient may feel "numbness," neuropathic pain is still present because the nerve is damaged from resection due to amputation.

I had a patient with diabetic neuropathy in the feet who experiences debilitating lancinating pain from an amputated toe. That agonizing pain flareup is the neuropathic pain, not nociceptive pain.

When it comes to the medical topic of peripheral neuropathy, all physicians, including podiatrists, must distinguish nociceptive pain mechanisms from neuropathic pain mechanisms. This can help improve diagnosis and treatment management.

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