Phantom Limb Pain

PLP is often described as tingling, throbbing, sharp, pins/needles in the limb that is no longer there. It occurs more commonly in upper extremity amputations than lower extremity and tends to be intermittent in frequency. Pain severity varies, and onset can be immediate or years afterward. It is important to try and distinguish PLP from RLP. The goal of the physical exam is to rule out the causes of RLP. First, the skin should be carefully inspected for evidence of wounds or infection. Sensation needs to be tested, along with looking for allodynia and hyperalgesia. The joint above the amputated limb should be examined for any signs of dysfunction. in terms of pain intensity, RLP usually is not severe, and features pressing, throbbing, burning, squeezing, and stabbing sensations.

The diagnosis of PLP pain is primarily a diagnosis of exclusion and heavily dependent on the patient's history.  Because of this lab tests are often not needed.  A complete blood count (CBC) can help rule out infection. An ultrasound can be ordered to look for neuromas as a possible pain generator. A psychology evaluation may be indicated if the patient is having a significant amount of extrinsic triggers that may be contributing to his or her pain.

Treatment, unfortunately, for PLP has not proven to be very effective. While treatment for RLP tends to focus on an organic cause for the pain, PLP focuses on symptomatic control.

Pharmacotherapy

• NSAIDs/Tylenol are the most commonly used treatment for PLP. [10]
• Opioids. Although observational and randomized controlled trials have demonstrated the effectiveness of certain opioids such as tapentadol for neuropathic pain [11] and PLP, they should be used in conjunction with antidepressants or neural modulating agents (i.e., gabapentin, pregabalin). [12]. Furthermore, their use in a condition of benign pain should be done with caution in order to avoid potential effects from tolerance and dependence. [13]
• Antidepressants are commonly used for addressing PLP. Amitryptiline, in particular, tends to be the tricyclic antidepressant (TCA) of choice as it has shown the best overall results, but other studies looking at nortriptyline and desipramine have shown them to be equally effective. However, most of these studies were not very rigorous and in a 6 week randomized trial between amitriptyline and placebo involving 39 patients, there was no significant difference between the two. [14] Duloxetine is another medication that has been showing some positive results. [15]  
• Anticonvulsants (gabapentin, pregabalin) have shown mixed results. [16]  The results overall for gabapentin have been conflicting, but a Cochrane review examining multiple studies did feel that the combined results favored Gabapentin over placebo. [17]
• N-methyl-d-aspartate (NMDA) receptor antagonist mechanism is not clear. These drugs have been shown to have benefit in pain syndromes, primarily with ketamine and dextromethorphan. Memantine has had mixed results. In the Cochrane review of 6 studies were included looking at Memantine versus placebo, there was no statistical improvement in pain between the groups [17].  Ketamine infusions have shown much better results than memantine, although the results between the two are not clear given their similar mechanisms. There is level 2 evidence to support the use of Ketamine infusions for the treatment of PLP [18].
• Beta-blockers (propranolol) and calcium channel blocker (nifedipine) show unclear data.
• Topical Analgesics like Capsaicin have been shown in some small studies to reduce hypersensitivity and PLP, but the evidence is still weak and requires more investigation. [19][20]
• Botulinum toxin type B injections have been used to treat hyperhidrosis (excessive sweating) in the post-amputation patient. Hyperhidrosis can not only hinder the use of a prosthetic but can adversely affect the course of both the phantom limb and RLP. Treatment of the hyperhidrosis with botulinum toxin type B injections has shown in several small studies to reduce RLP, PLP, and sweating. [21]  Botulinum toxin type A is also being investigated, but so far has not been shown to decrease pain intensity compared to lidocaine/methylprednisolone. [17]
• Local anesthetics. A Cochrane review looked at two studies examining the effectiveness of local anesthetics, lidocaine infusion at 4mg/kg and bupivacaine 0.25% as a contralateral myofascial injection, in treating PLP in randomized trials. The one-time contralateral myofascial injection of 1cc bupivacaine 0.25% showed significantly improved pain relief in the 8 patients studied [22].  Lidocaine infusion was not found to have any significant improvement compared to placebo [23]
• Other pharmacological strategies such as calcitonin have no clear evidence.

Non-Pharmacologic Options

• Transcutaneous electrical nerve stimulation (TENS) shows moderate evidence supporting its use. Low-frequency and high-intensity are thought to be the most effective for PLP. It may also be used to help relieve RLP.
• Mirror therapy. A small randomized trial of mirror therapy in patients with lower leg amputation showed a significant benefit of PLP.[24] Another study was minimally helpful.
• Biofeedback shows limited evidence.
• Acupuncture research is still ongoing.
• Spinal cord stimulation (SCS) is obtained through an implantable device that stimulates transdural the dorsal columns of the spinal cord. It is often an effective therapy for PLP. 
• Apart from TENS and SCS, other neuromodulation approaches such as peripheral nerve stimulation (PNS) can be helpful for both PLP and RLP.
• Virtual and Augmented Reality has provided some novel opportunities to utilize technology as an advanced form of "mirror therapy".  Researchers have been able to program myoelectric movement patterns from the RLP into the virtual or augmented reality headsets and then correlate those movements to the movements of the "complete" limb in the virtual world.  This has been shown in several case studies to be effective treatments for PLP, but no large studies have been conducted. [25] [26]
• A sympathetic block may also help.
• Stump revision

• Septic arthritis
• Osteomyelitis
• Foreign body reaction
• Neuroma
• Arthritis

PLP is very complex and difficult to treat. It is best managed by an interprofessional team The first treatment is usually conservative and should include nonpharmacological and nonsurgical methods. The prosthetic professional should assess the stump and train the patient in the use of the prosthetic device. A mental health nurse and psychotherapist should help ease anxiety and depression. If this fails, The pharmacist should work with the clinician to select an appropriate agent, as well as educate the patient on the different pharmacological agents available, their effectiveness and adverse effects. A pain specialist should be involved as well

There is no one treatment that works reliably or consistently in all patients. Most patients are prescribed multiple agents to control pain, but tragically, this polypharmacy also has serious adverse effects that tend to lower compliance. Patients with PLP often doctor shop and try many types of conventional and non-conventional therapies to relieve the pain.

A pain referral should be ordered and the patient's HR-QOL should be improved. 

Patient education is key and members of the team should communicate with each other so that the patient is provided with optimal treatment. The outcomes for most patients are guarded and the quality of life is poor.