A Closer Look At Evolving Treatments For Phantom Limb Pain

Start Page:

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

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

   Hsu and Cohen report that the spinal mechanisms for post-amputation pain are theoretically centered on functional changes in the dorsal horn of the spinal cord after deafferentation from peripheral nerve injury.9 Iacono and colleagues report that the loss of afferent input to the dorsal horn leads to decreased impulses from brainstem reticular areas, which normally exert inhibitory effects on sensory transmission.11 Reports from both Davis and Jensen and their respective coworkers note that the absence of inhibitory effects for sensory input arising from the missing peripheral body part cause an increased autonomous activity of dorsal horn neurons, in effect becoming “sensory epileptic discharges.”9,12,13 The role of spinal mechanisms is validated by the fact that both anticonvulsants, as well as lesions placed in the substantia gelatinosa, are effective in treating phantom pain.9,14

   Cortical reorganization is the most cited reason for the cause of phantom limb pain in recent years.8 These cortical areas representing the amputated extremity are taken over by the neighboring representational zones in both the primary somatosensory cortex and the motor cortex.8,15 Research has found the extent of cortical reorganization to be directly related to the degree of pain and the size of the deafferentiated region.8

   An amputation severs peripheral nerves, resulting in massive tissue and neuronal injury, and causing disruption of the normal pattern of afferent nerve input to the spinal cord.8 The process of differentiation follows this and the proximal portion of the severed nerve sprouts to form neuromas.16 During this process, there is an increased accumulation of molecules enhancing the expression of sodium channels in these neuromas that result in hyperexcitability.17

   Flor and colleagues report that this abnormal peripheral activity is theoretically a potential source of stump pain, including phantom limb pain.16 To validate the contributory influence of this mechanism to phantom limb pain, clinical studies have reported a reduction of phantom pain with drugs blocking these identified sodium channels.18,19 Another proposed mechanism is that the increase in N-methyl-D-aspartate (NMDA) receptor activity results in a change in neuronal firing of the nociceptive neurons, exacerbating phantom limb pain.20

   Despite Berger and Bacon’s report that stress, anxiety, exhaustion and depression theoretically exacerbate phantom limb pain, the recent literature has not supported the psychogenic origin mechanism of phantom limb pain.21 Visual-proprioceptive dissociation involves a disconnect between proprioceptive memory, which refers to the awareness of limb position, and visual perception.22 This particular theory describes phantom limb pain as occurring because proprioceptive memory causes the neurons to remain in an active state after amputation.

   A notable limitation to the psychogenic mechanism is that most research on the relationship between psychological symptoms and phantom limb pain is based on either retrospective and/or cross-sectional designed studies rather than longitudinal designed studies.8 Therefore, this limits the inference that we can derive from these types of studies.8

A Guide To Pharmacologic Treatments For Phantom Limb Pain

Treatment of post-amputation pain is very challenging because the underlying mechanisms are multifactorial in nature (see “A Guide To Mechanism-Based Treatment Modalities For Postamputation Pain” below at right). Given that mechanistic-based pain treatment is generally acknowledged to be superior to etiologic-based treatment, the difficulty in identifying a discrete mechanism(s), which one can address directly, results in corresponding barriers to treatments. Given that multiple cellular, neurochemical and molecular changes underlie both the peripheral and central reorganization phenomena that occur in the post-amputation period, pharmacological interventions are a natural choice for the treating clinician.

image description image description

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.

Reply to this comment »
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.

Reply to this comment »

Post new comment

  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

More information about formatting options

Enter the characters shown in the image.