A Closer Look At Evolving Treatments For Phantom Limb Pain

Robert G. Smith, DPM, MSc, RPh, C.Ped

   There are currently no guidelines for the management of phantom limb pain. When choosing pharmacotherapy for patients with phantom limb pain, the clinician must consider chronicity, route of administration and side effects.9 Several categories of medications for which there is a clinical base evidence in the treatment of phantom limb pain are: anticonvulsants, antidepressants, opioids, injection therapies and NMDA receptor antagonists (see “A Guide To Pharmacotherapy Treatments For Phantom Limb Pain” below at left).

   Anticonvulsants. Anticonvulsants have long been a mainstay in the treatment of neuropathic pain. On the other hand, specific studies examining anticonvulsants and their beneficial outcomes when treating phantom limb pain are limited.
Gabapentin (Neurontin, Pfizer) is an anticonvulsant that is structurally similar to gamma-aminobutyric acid (GABA). Its mechanism involves high-affinity binding to the alpha-2/delta-1 subunit of voltage-gated calcium channels.23 One study concluded that gabapentin effectively improved phantom limb pain at doses ranging from 300 to 2,400 mg per day.24 However, a recent study by the Department of Veterans Affairs found no significant difference in pain intensity for gabapentin versus placebo.25

   Although studies have yielded mixed results, gabapentin is often a first-line treatment in clinical practice. Patients generally tolerate gabapentin well. However, it is important to monitor renal function and make dosage adjustments as well as significant side effects reported in clinical studies include: somnolence, dizziness, headache and nausea.24-26

   Carbamazepine (Tegretol, Novartis), which can also manage phantom limb pain, inhibits sodium-channel activity. Carbamazepine doses of 400 to 600 mg per day have been effective for treating stabbing and lancinating pain associated with phantom limb pain.8,27 In preliminary studies, the anticonvulsants pregabalin (Lyrica, Pfizer) and oxcarbazepine (Oxtellar, Supernus Pharmaceuticals) have demonstrated some promise for treatment of phantom limb pain.8,28-30

   Antidepressants. Tricyclic antidepressants are among the most commonly used medications for various types of neuropathic pains to include phantom limb pain. Tricyclic antidepressants produce their effect by blocking several receptors, including the norepinephrine and serotonin reuptake pumps, sodium channels, as well as the muscarinic acetylcholine, alpha 1, histamine 1 and GABA receptors.

   Although research has shown tricyclic antidepressants to provide some benefit in the treatment of phantom limb pain, their use is limited by their negative adverse effect profile to include dry mouth and dizziness.31 Other noted adverse drug reactions include cardiotoxicity, orthostasis, tachycardia, arrhythmias, insomnia, dizziness, weight gain and anticholinergic effects.

   Serotonin-norepinephrine reuptake inhibitors (SNRIs), another antidepressant class, have shown promise as a treatment option for neuropathic pain and phantom limb pain. The role of norepinephrine in pain modulation involves its action on alpha-2a adrenoceptors in the spinal dorsal horn, which reduces nociceptive signals to the brain.32

   In a review of clinical trials comparing SNRIs with placebo in the treatment of neuropathic pain, the National Institute for Health and Clinical Excellence concluded that duloxetine (Cymbalta, Eli Lilly) and venlafaxine (Effexor, Pfizer) lessen the intensity of neuropathic pain.33 Empowered with this data, the treating podiatric clinician may want to use these agents for phantom limb pain.


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

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.

Add new comment