Phantom limb pain and residual limb pain

Phantom limb pain is one of the large class of nerve pain, also known as neuropathic pain, and occurs after amputation of a body part. Affected patients experience pain in the area of the amputated body part that is described as cutting, stabbing, burning, or cramping. It is a neurological disorder resulting from changes in the nervous system, rather than a psychiatric disorder as previously thought.

Approximately 50–80% of patients with an amputated body part can develop phantom limb pain *. However, the intensity, length and frequency of the pain varies greatly between patients. For many patients, the pain is transient and does not result in a major reduction in quality of life.

Phantom limb pain can occur either immediately or even years after amputation. The literature describes two time points at which phantom limb pain mainly occurs: the first within one month and the second one year after amputation. *

Although the condition has been recognized since the 16th century, phantom limb pain remains a puzzling and difficult-to-treat condition to this day. The exact causes of phantom limb pain are not yet fully understood.

Initially, phantom limb pain was classified as a psychiatric disorder. However, as medical knowledge deepened, it gradually became clear that changes in the nervous system occur after amputation (both peripheral and central) and that these changes are at least partially responsible for phantom limb pain.

Peripheral changes include neuronal hyperactivity, which is increased activity of nerve cells in the area of the stump.

Central changes include remodeling processes in the brain and sensory changes in the area of the spinal cord *.

Additionally, pain before amputation and psychological factors seem to play an important role in the development of phantom limb pain. However, none of these factors can independently explain the phenomenon. Currently, several mechanisms are thought to be responsible for the development of phantom limb pain.

Generally, the diagnosis is made by an interdisciplinary team of pain specialists, surgeons and physiotherapists. The patient is asked about the onset, intensity and frequency of pain symptoms, known pain triggers and previous treatment measures. In addition, the patient is advised to keep a pain diary. It is important to rule out residual limb pain and – if this is present – to treat the cause of the stump pain.

Currently, approximately 50 treatment options for phantom limb pain are suggested in medical literature *. However, none of these therapies is recognized as independently effective or significantly superior to the others. The treatments described each target a single mechanism. However, because multiple mechanisms contribute to the development of phantom limb pain in each patient, a combination of therapies is usually recommended to affected individuals.

Therapy is primarily based on the severity and duration of the pain. The main focus is on drug therapy. The most commonly used drug classes are:

• non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or acetaminophen
• opioids such as morphine or tramadol
• antidepressants such as amitriptyline
• anticonvulsant therapeutics such as carbamazepine, gabapentin or pregabalin
• local anesthetics such as lidocaine
• ketamine

As a rule, drug therapy is combined with complementary therapy. Options are:

• physical therapy such as baths or massages
• transcutaneous electrical neurostimulation (TENS) *
• mirror therapy (the part of the body that is still present is mirrored so that the patient gets the impression that the reflection is the amputated part of the body) *
• neural therapy such as trigger point infiltrations or nerve blocks
• acupuncture
• cognitive behavioral therapy

Despite drug and adjuvant therapy, there are cases in which no satisfactory pain relief is achieved. In such patients with severe and difficult-to-treat pain, a neurostimulation procedure is considered. There are invasive and non-invasive stimulation procedures:

Non-invasive stimulation procedures

• repetitive transcranial magnetic stimulation (rTMS)

Invasive stimulation procedures in the area of the brain

• deep brain stimulation (DBS)
• motor cortex stimulation (MCS)

Invasive stimulation procedures in the area of the spinal cord

• spinal cord stimulation (SCS)
• dorsal root ganglia stimulation (DRG)

Repetitive transcranial magnetic stimulation (rTMS)

Repetitive transcranial magnetic stimulation (rTMS) is a diagnostic and therapeutic procedure that uses magnetic fields to stimulate or inhibit specific regions in the brain. Several studies have investigated rTMS. The largest of these studies, with data from 54 patients, showed a greater than 30% reduction in pain intensity 2 weeks after therapy *.

Deep brain stimulation (DBS)

With regard to deep brain stimulation (DBS), several studies showed that patients with nerve pain benefit well from this intervention *, *. Pain reduction is 50–60% one year after the procedure *. During the intervention, electrodes are inserted deep into different core areas of the brain via a burr hole.

Motor cortex stimulation (MCS)

Motor cortex stimulation (MCS) is a neuromodulation procedure that has shown efficacy in patients with severe, refractory neuropathic pain such as phantom limb pain. In this procedure, an electrode is placed on the brain surface over the motor area via an opening of the skull (craniotomy). Although the studies were carried out with only a few patients (12 and 3 patients respectively), there was a clear success in terms of pain relief of about 70% after 2 years. *, *.

Spinal cord stimulation (SCS)

Both spinal cord stimulation and dorsal root ganglion stimulation have shown good results in the spinal cord area. Due to the assumption of sensory changes in the area of the spinal cord after an amputation, spinal cord stimulation (SCS) has been used for the therapy of phantom limb pain since 1970. In a 2012 study, SCS was performed in patients with residual limb and phantom limb pain. It showed up to 80–90% pain relief at 5 to 20 years in 42% of patients (5/12). The remaining patients were not followed up (2/12) or did not benefit from SCS. The reasons for nonresponse to therapy were:

• new onset of pain that was not present at SCS implantation
• plate rupture
• painful stimulation in one patient after 19 years of good response
• decreaed stimulation effect *

Not all patients in the study underwent a test phase beforehand, which also partly explains the non-response. A good indication and the performance of a test phase are very important in every patient.

Dorsal root ganglia stimulation (DRG)

Dorsal root ganglia stimulation (DRG) showed equally good results, with pain relief of 73–100 % *, *. However, these studies have examined both patients with residual limb pain and patients with phantom limb pain.

Stump pain fundamentally differs from phantom limb pain, both in terms of its mechanisms of origin and its therapy. Stump pain is pain that occurs directly at the amputation stump, often due to wound pain, bruising, infection, or poorly adapted prostheses. Stump pain usually occurs shortly after amputation. However, about 5–10% of patients suffer from chronic stump pain after amputation *.

In contrast to phantom limb pain, where pain relief by means of medication, physiotherapy, massage or nerve stimulation plays the most important role, in the case of stump pain the elimination of the underlying cause is essential for successful treatment.

Stump pain is perceived as stabbing and extremely severe by the patient. In the first few weeks after an amputation, they are part of the normal healing process. In the acute phase, patients often receive high doses of opiates or ketamine. However, the "gold standard" in this phase is regional anesthesia, which is achieved either via peripheral nerve block or epidural infusion *.

If stump pain persists weeks after an amputation, it is important to look for a cause of the pain. The most common causes are:

• infections
  Inflammatory changes in the area of the stump (swelling, redness, wound healing disorders, pus discharge). The infection can be superficial, but can also reach deep to the bone. In such situations, rapid diagnosis is very important. This is done by blood sampling (increased inflammation values), blood cultures, X-rays, magnetic resonance imaging (MRI) or, if necessary, bone scintigraphy. Antibiotic therapy should be initiated as soon as possible. *.
• amputation neuroma
  Amputation neuromas are benign nodular formations that develop as a reaction of the severed nerves at the nerve endings. The neuromas regress weeks after amputation. Patients with these changes experience pinpoint pain in the area of the stump. The diagnosis can be made either by ultrasound examination of the residual limb or by means of an MRI *. In t–he case of neuromas, conservative measures are initially recommended, such as massage, analgesic therapy, transcutaneous electrical neurostimulation (TENS), or infiltrations. If these do not help sufficiently, neuromere resection can be considered *.
• heterotopic bone formation
  Here, soft tissue in the area of the residual limb is converted to bone tissue. This is the case in 63% of amputations after an accident *. The exact cause is not known. There is also no generally accepted therapy so far.
• wound dehiscence and bruising
  Wound dehiscence (softening of the wound edges) and bruising in the area of the residual limb can be diagnosed clinically or by imaging. They are usually corrected in a minor surgical procedure.
• poorly fitting prostheses
  Poorly fitting prostheses need to be changed or readjusted if they are causing stump pain.