Clinical Pearls on Phantom Limb Pain

First described more than 500 years ago, phantom limb pain (PLP) is a common disorder today; as many as 50% to 80% of patients who undergo amputation report experiencing pain in the missing appendage.¹ Although it is easy to recognize and diagnose, its cause remains unclear, and it can be difficult to manage successfully. Perhaps that's why health care professionals often do not address it. A survey by Hanley and colleagues,² for example, found that 53% of patients with PLP and 38% with severe PLP had never been treated for the disorder.

Why this problem develops in certain patients remains unclear, although animal studies indicate that there may be a genetic predisposition to PLP.³ PLP most commonly occurs after the amputation of an extremity, but it also has been reported after surgical removal of other parts of the body, most notably after a mastectomy.

At one time, PLP was thought to be primarily a psychological problem that reflected both the patient's grieving over the loss of the limb and his or her desire to believe that the limb was still present; however, psychological factors do not appear to be the primary cause. Ephraim and colleagues⁴ found the presence of depression to be a predictor of the severity of PLP, although it was similarly associated with residual limb and back pain in amputees.

CONCEPTS OF CAUSATION
Current concepts of causation center primarily on the role of the peripheral and CNS.⁵ Amputation results in a disruption of normal peripheral nerve activity. The traumatic injury to the nerves may cause abnormal ectopic discharges that are perceived as pain at the level below which the nerves were severed. Formations of neuromas in the remaining portion of the limb also may play a role, although it has been noted that PLP frequently occurs before there has been sufficient time for neuromas to appear. Activation of the sympathetic nervous system is also a possible cause.

Centrally, changes may occur in both the spinal cord and brain following amputation. Injuries to the peripheral nerves can result in changes in synaptic responsiveness in the dorsal horn that can lead to increased neuronal excitability there and decreased inhibitory processes.⁶ It appears that following amputations, there may be changes in the brainstem, thalamus, and cortex caused by abnormal peripheral input. However, it is unclear whether these changes are involved in the causation of PLP or are secondary to it.

Since there are no physical changes in PLP, the diagnosis is made solely on the basis of the patient's self-report. Because the presence of pain in a missing body part seems irrational, it is important to assure patients who fear for their mental health that PLP is a very real phenomenon. It is also important that the clinician diagnostically differentiates PLP from stump pain, which commonly occurs after amputation and is often much easier to manage.

When describing PLP, the patient will report a variety of sensations, including burning, shooting, and aching pains as well as tingling and pins-and-needle sensations. The pain is usually intermittent and most often felt in the distal parts of the missing limb.¹

MANAGING THE PAIN
There is no single best treatment of PLP. Multiple therapies have been used with mixed success. The number of good controlled studies on the topic is limited. Unfortunately, there are no factors for predicting which therapy is likely to benefit a particular patient.

The apparent neuropathic nature of PLP would suggest that antidepressants, anticonvulsants, and other medications used for neuropathic pain would be most effective. However, Ephraim and coworkers⁴ found that most patients are treated with acetaminophen, NSAIDs, and opioids.

As with any neuropathic pain, the antidepressants that affect both the serotonergic and noradrenergic systems provide the strongest analgesic effects. In a recent randomized, placebo-controlled study, Wilder-Smith and colleagues⁷ reported that 25 of 30 patients with PLP responded to treatment with amitriptyline (Elavil), and 22 of 33 patients responded to the serotonin/norepinephrine reuptake inhibitor (SNRI) and a weak opioid tramadol (Ultram), compared with only 2 of 37 patients who responded to placebo. If tricyclic antidepressants cannot be tolerated or their use is contraindicated, consider either the SNRI venlafaxine (Effexor) or duloxetine (Cymbalta) as an alternative; but be aware that studies on their use for the treatment of PLP have not been published. Studies indicate that at least 2 anticonvulsants, gabapentin (Neurontin) and topiramate (Topamax), may be beneficial for PLP.^8,9

Another useful medication for neuropathic pain in the treatment of PLP is the lidocaine patch (Lidoderm). This medication does not cause significant adverse effects and, therefore, can be used safely even in patients with severe medical problems.

Psychologically based modalities also may provide relief. Therapies such as biofeedback and hypnosis may directly affect the physiologic processes involved in the pain. Other therapies that may be beneficial include peripheral nerve blocks, epidural infusion of analgesic agents, transcutaneous electrical nerve stimulation, and acupuncture. Surgical interventions-including sympathectomy, rhizotomy, cordotomy, and most recently, deep brain stimulation-also have been used.¹⁰

Editor's Note: A version of this article was published in the April 2006 issue of Psychiatric Times.

STEVEN A. KING, MD, is clinical professor of psychiatry at the New York University School of Medicine in New York City.

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