Pain Management Strategies for Phantom Limb Pain

RESEARCH ANALYSIS

Pain Management Strategies for Phantom Limb Pain

Tien Vu, BS

Sidney Kimmel Medical School at Thomas Jefferson University

SUMMARY POINTS:

-       Phantom Limb Pain (PLP) is a chronic and intractable condition often occurring after amputation, with up to 78% of amputees experiencing this condition.

-       There are several theories and models to explain the underlying mechanisms of PLP, such as Cortical Remapping Theory/Maladaptive Plasticity Model and the Neuromas and Dorsal Root Ganglion Theory. However, there is mixed evidence supporting each theory and further research is needed.

-       Currently, there are several treatment strategies to address PLP, including pharmacotherapeutics and visual feedback approaches (Mirror Therapy, Virtual Reality). Mirror Therapy is most often used to compare to other approaches; however, it is unclear if it has higher efficacy than other approaches.

ANALYSIS

Background

The term “phantom limb,” which refers to the sensations of the missing limb’s presence, was first coined by American neurologist Silas Weir Mitchell in 1871 as ‘spirit limbs’ haunting soldiers (1). This neurological phenomenon is prevalent among amputees, occurring in up to 78% of cases, with most sensations being painful (2). However, phantom limb experiences are not exclusive to amputees, as they can also be observed in individuals with congenital limb deficiencies.

While similar, phantom limbs should not be mistaken for Phantom Limb Pain (PLP), which is painful sensations derived from phantom limbs. Individuals born without limbs or those who have experienced spinal cord or peripheral nerve injuries can also experience phantom pain. This pain can be sharp, burning, cramping, or aching and is often difficult to treat (3). Unfortunately, PLP is generally intractable and chronic, with the patients’ condition rarely improving in treatment. Symptoms can be lessened, however, by temporarily reducing pain for patients. Chronic pain can interfere with patients’ lives and work, presenting numerous challenges (4).

Although PLP is typically categorized as neuropathic pain, various models attempt to explain its underlying mechanisms. One of the most popular explanations for PLP is the Cortical Remapping Theory, or Maladaptive Plasticity Theory. The brain is believed to respond to limb loss by reorganizing somatosensory maps. Therefore, this theory suggests that PLP arises because of plastic changes to the primary somatosensory cortex (5). When the brain’s primary sensorimotor cortex, or the homunculus, no longer receives input from the amputated limb, signals from another body part, such as the lips, begin to take over that area. This change in the cortical representation is thought to be the cause of the pain (1,7).

Figure 1. Cortical contributions to somatosensory map, and how reorganization of such map post-amputation may lead to PLP.

However, other studies have challenged this explanation. One found that cortical regions representing the amputated limb remained structurally and functionally intact, with some even showing stronger representation rather than weaker. No evidence of cortical remapping was observed (6). Thus, the precise mechanism and role of the homunculus in PLP remain greatly debated. Further research with larger sample sizes and diverse representations of amputated limbs is needed to clarify the disparities as well as determine if cortical remodeling is a driver or byproduct of the pain.

Another theory to explain PLP is centered on neuroma formation and the dorsal root ganglion (DRG). According to this theory, DRG axons are disconnected from their distal targets after amputation, leading to inflammation and formation of neuromas in the resulting residual limb. Hyperexcitable loci in the injured axons may generate spontaneous activity, which is propagated to the spinal cord, resulting in pain (3).

Findings

In analyzing PLP, there are various factors to be considered that can contribute to different presentations. Contributing factors include time after amputation, site of amputation, pre-amputation pain levels, emotional stress, tiredness, weather changes, previous swelling not healed, infection, poor blood flow, and many others (2). Treatment is often based on the individual’s level of pain, with personalized tailoring dependent on the patient's reported outcomes. Some of the treatments include pharmacotherapeutics, visual feedback approaches like ‘phantom exercises’ (mirror therapy and virtual reality), TENS (transcutaneous electrical nerve stimulation), biofeedback and behavioral methods (cognitive behavioral therapy, hypnosis, acupuncture, relaxation techniques), and surgery.

For pharmacotherapeutic treatments, anti-seizure medications such as gabapentin and pregabalin are often used to reduce the frequency and intensity of neuropathic pain, with mixed results in studies (8, 9). Opioids have shown evidence in reducing cortical remapping as well as >50% pain reduction in 42% of patients in one study; however, a larger sample size is needed to confirm these findings (10). Additionally, the potential for dependency and side effects such as nausea, vomiting, and constipation remain a risk when prescribing opioids to treat chronic neuropathic pain such as PLP. Another study found that lidocaine injections into DRG for a patient can transiently relieve PLP, thereby potentially supporting the mechanisms of neuroma formation previously mentioned and creating a possible avenue for more precise pain relief (11). While NSAIDs were reported in a cross-sectional study to be the most common pain medication used to treat PLP, they were not very effective, with the majority of survey participants rating only opioids and chiropractic care as moderately to extremely helpful (12).

Visual feedback approaches, such as mirror therapy, rely on the activity of mirror neurons. It is believed that patients can alleviate phantom limb pain (PLP) by moving their intact limb in front of a mirror to create a visual representation of the missing limb, while simultaneously attempting to move the phantom limb. Although the underlying mechanism is not well understood, mirror therapy has yielded mixed results; one case report describes successful alleviation of PLP (13), whereas another study reports increased phantom limb movements without a corresponding reduction in pain (14). Virtual reality (VR), similar to mirror therapy, also utilizes visual feedback by stimulating both the intact and missing limbs. Participants wear VR goggles to visualize a representation of the missing limb, and performing phantom limb exercises has been theorized to help reduce pain. However, in the past five years, only one randomized controlled trial has investigated the efficacy of VR for PLP, and its findings do not strongly support VR as an effective treatment (15,16).

Other treatment approaches, such as TENS, biofeedback and behavioral methods, and surgical interventions, are not well studied and are largely limited to case reports (2).

Discussion

PLP remains a difficult condition to treat, with many potential underlying mechanisms and multiple theories to explain its etiologies. Thus, studying how these theories intersect with each other may be the key to understanding the mechanisms more. Current published literature shows a need for further randomized controlled trials to examine and compare the efficacy of different treatment approaches, as there is no clear evidence of any specific treatment showing significant clinical attenuation of PLP.

REFERENCES

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