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their amputation demonstrated that higher amputation levels were associated with decreased prosthetic use
[11]
while less intense residual limb pain was associated with greater daily prosthetic use . Therefore, post-
amputation pain is not only simply unpleasant, but also directly affects patient function.

POST-AMPUTATION PAIN
Prevalence
Pain significantly impairs the post-amputation patient. In fact, among amputees with chronic pain, it is
often not the underlying condition (i.e., amputation of the limb) that primarily limits the individual, but
[2,9]
rather the chronic pain they experience . Unfortunately, chronic pain is commonplace among amputees.
Advances in the measurement of pain, including the validated Patient-Reported Outcomes Measurement
Information System (PROMIS) pain interference and pain behavior scores, have been integral in better
understanding the significance of pain on patients’ lives [12,13] . PROMIS is a National Institute of Health-
funded initiative to develop and validate patient-reported outcomes, including over 300 different measures
of physical, mental, and social health typically used for populations with chronic conditions . There are
[13]
several types of amputation-related pain, including phantom limb pain (PLP), defined as pain in the limb
that is no longer present, phantom limb sensation/telescoping, residual limb pain, and back pain . A cross-
[14]
sectional survey through the Amputee Coalition of America in which 914 amputees were interviewed over
the telephone found that 95% of amputees had some daily pain . The most common pain type was
[2]
phantom limb pain (79.7%), residual limb pain (67.7%), followed by back pain (62.3%) . A systematic
[2]
review of twelve cross-sectional and three prospective studies of traumatic and atraumatic amputees also
reported phantom limb pain incidence as high as 82% at one-year post-amputation and a lifetime
prevalence as high as 87% . Even decades after amputation, phantom limb pain, and residual limb pain
[15]
continue to trouble patients. In a survey of 21 patients who underwent lower limb oncological amputation
with a median follow-up duration of 41 years, seventeen reported phantom limb and back pain, fifteen
residual limb pain, all with median pain scores five and above on a scale of 1-10 . Post-amputation pain is,
[11]
therefore, a ubiquitous and long-lasting complication of the operation.

Causes of chronic pain
While chronic pain is not yet fully understood, mechanistically, it is due to afferent input from the
peripheral nervous system. A randomized, double-blind, placebo-controlled crossover study of lidocaine
compared to placebo saline injection in amputees demonstrated expected outcomes of improved pain,
[16]
especially phantom limb pain, in those who received the lidocaine block . The causes of the pain are
thought mainly from chronic nerve compression and neuroma. Chronic nerve compression typically occurs
[17]
with major nerves at common entrapment sites . Neuromas are classified as neurotmesis or Sunderland
5th degree peripheral nerve injury . When peripheral nerves are injured, the distal end undergoes
[18]
Wallerian degeneration. The proximal axon is unable to progress to its distal target, and the unorganized
[18]
fascicular overgrowth results in scarring, thereby forming a neuroma . Psychological factors are also
thought to play a major role in both acquisition and maintenance of pain symptoms .
[19]
Symptomatic neuroma
[18]
Neuromas were first described by Abroise Pare in 1634, who treated the symptoms with massage .
Neuropathic pain associated with neuroma can be classified into four types: spontaneous pain, pain with
pressure over the neuroma, pain on movement of adjacent joints, and dysesthesia or hypersensitivity with
light skin touch . Histological features and mechanisms of formation have been explored in several animal
[20]
studies. A study of Sprague Dawley rat forelimb amputations demonstrated a progression of nerve injury
from degenerating axons to axonal spouts to unorganized bundles of axons which grow into muscles and
nearby structures and eventually into fibrotic tissue, ultimately forming a neuroma [Figure 1] . There are
[21]
multiple theories on why neuromas cause pain. Proposed mechanisms include repetitive mechanical