Phantom Limb Pain
A review by Lindsey Tucker, MD
Incidence
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An estimated 1.7 million people in the US are
living with limb loss.
Each year 158,000 persons undergo an
amputation
The incidence of phantom pain is 60-80%
among amputees.
Independent of adult age, gender or location or
side of amputation (less common in children or
congenital amputees)
Onset and Duration
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Several studies have shown that 75% of patients
with PLP develop pain within the first few days
after amputation.
One study of 58 amputees found incidence of
PLP to be 72%, 65% and 59% after 1 week, 6
months and 2 years. (Jensen, et al 1985)
Another study of 56 amputees showed that
although the incidence and intensity of pain
remained constant, the frequency and duration
of pain attacks decreased significantly.
(Nikolajsen, et al 1997)
Character and association
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Phantom pain is usually intermittent; only few
patient’s are in constant pain.
Pain is primarily located in distal parts of the
missing limb.
Few case reports suggest that pre-amputation
pain may persist as PLP, but this is not the case
in most patients.
Phantom pain is more frequent in patients with
long-term stump pain, and decreases with
resolution of stump-end pathology
Mechanisms of Phantom Pain
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Following a nerve cut, formation of neuromas
are seen, which show spontaneous and
abnormal evoked activity following mechanical
and chemical stimulation. (Amir, et al 1993)
Percussion of stump/neuromas induces stump
and PLP; increased activity of afferent C fibers
(Nystrom, et al 1981)
Perineuromal injection of gallamine produces
PLP, injection of lidocaine blocks PLP. (Chabal,
et al 1981)
Spinal Plasticity
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After nerve injury, C-fibers and A delta-afferents
gain access to secondary pain signaling neurons
(mediated by glutamate and neurokinins). This is
manifested by mechanical hyperalgesia and
expansion of peripheral receptive fields.
(Doubell, et al 1999)
Increased activity of NMDA receptor; central
sensitization can be reduced by NMDA
antagonists such as ketamine. (Eichenberger, et
al 2008)
Anatomical reorganization
Peripheral nerve damage can lead to
degeneration of C-fiber afferent terminals
in laminae II. As a result, central terminals
of Aβ-mechanoreceptive afferents (which
normally terminate in laminae III and IV)
sprout into laminae I and II. (Woolf, et al
1992)
 Ultimately, this results in increased general
excitability of spinal cord neurons.
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Sympathetic nervous system role
Application of norepinephrine or activation
of post-ganglionic sympathetic fibers
excites and sensitizes damaged (not
normal) nerve fibers. (Devor, et al 1994)
 Sympatholytic block can abolish
neuropathic pain, but pain can be
rekindled by injection of norepinephrine
under the skin. (Torebjork et al 1995)
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Cerebral reorganization
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One study of adult monkeys revealed cortical
reorganization in which the mouth and chin
invade cortices corresponding to arm and digits.
(Dotrovsky, et al 1999)
In humans, similar reorganization has been
observed using magnetoencephalographic
techniques and there was a linear relationship
between pain and degree of reorganization (flor,
et al 1998)
Treatment: A
Multidisciplinary Approach
TENS
Acupuncture
Bio-feedback
Hypnosis
Massage
Ultrasound
ECT
TCA
Anticonvulsants
Lidocaine
Opioids
NMDA antagonists
clonidine
Nerve blocks
Neurectomy
Stump revision
Rhizotomy
Cordotomy
Lobectomy
Sympathectomy
Spinal cord stim
Brain stimulation
Medication trials
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TCA’s and sodium channel blockers are currently
considered the drug treatments of choice for neuropathic
pain, but a 2004 study of 39 patients demonstrated no
benefit of TCA’s over placebo in PLP after 6 weeks.
(Robinson et al 2004)
One study showed that mexiletine produced pain relief in
18 of 31 patients with PLP. (Davis 1993)
Opioids (MST) produced pain relief in 42% of patients
and showed evidence of reduced cortical reorganization
in 12 patients with PLP. (Huse E 2001)
There have been mixed results in studies using
memantine to treat chronic pain, but it may be successful
in treating PLP if initiated in early post-amputation
period. (Hackworth, et al 2008)
Adjuvant therapies
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TENS has reduced PLP in multiple placebo
controlled trials.
Mirror box therapy: persons with amputated limb
use either a mirror or mirror box to reflect an
image of the intact limb. It is hypothesized that
this works by preventing cortical restructuring.
One RCT of 22 patients showed 100% of
patients with MBT showed decreased pain after
4 weeks. (Chan BL 2007)
Mirror box therapy
Prevention
It was hypothesized that pre-amputation
pain created an imprint in the CNS such
that it could cause pain after the
amputation.
 Studies are mixed, but some show that the
incidence of PLP is decreased at 6 and 12
months if an epidural is placed preoperatively and continued 3-7 days postop.
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