Transcript Document

Phantom Limb Pain:
Current Theories and Evidence
Based Treatments
Christopher V Boudakian, DO PGY-4
Rusk Rehabilitation
NYU Langone Medical Center
Objectives
•Identify the definition and characteristics of phantom pain
•Understand the current theories in the etiology and
pathophysiology of phantom pain
•Identify current evidence-based treatments for phantom
pain
What is phantom limb pain?
• The concept, first introduced by French military surgeon Ambrose Pare
in the mid 16th century, is pain that is perceived in a region of the body
that is no longer present.
• Later expanded by Silas Weir Mitchell in the mid 19th century who
coined the term “phantom pain”
• Traditionally described as two separate phenomena
• Perhaps a spectrum disorder?
• In 1998, Weinstein proposed phantom sensations can be divided into 3
categories: kinetic sensations, kinesthetic components, and
exteroceptive perceptions
3 categories of sensation
• Kinetic sensations are the perception of movement, both spontaneous
and willed
• Kinesthetic components refer to the size, shape, and position of the
missing body part
• Exteroceptive perceptions include touch, pressure, temperature, itch,
and vibration
•Pain described in this category, however, distinguished by greater
intensity
Characteristics of phantom pain
• Seen in both patients with congenital and acquired limb deficiency.***
• Symptoms not limited to the limbs
•Reports of phantom sensations and pain emanating from less
common regions of the body including breast, nose, teeth and also
visceral organs including rectum, uterus, and bladder.
• Recent studies report 50 to 85% of patients with limb loss experience
phantom pain.
• This is in contrast to earlier studies which report rates under 10%
• Incidence rates have been shown to be independent of gender, age,
and location/level of amputation.
• Not likely affected by mechanism, elective vs traumatic1
Characteristics of phantom pain
• Correlations with residual limb pains remain unclear
•Kooijman et al. (2000) and Nikolajsen et al. (1997) reported positive
correlation between phantom pain and residual limb pain.
• Estimates show 50% of people with acquired amputations experience
phantom pain in the first 24 hours and an additional 25% in the in the
first week following limb loss1
• Uustal and Meier report most people with amputations do not
experience significant pain beyond 3 months.
Characteristics of phantom pain
• Often described as burning,
cramping, electrical shocks,
severe itching, or stabbing
• Episodes may last seconds to
hours.
Theories of phantom pain
• Despite numerous attempts to classify and define phantom pain, the
pathophysiology and etiology of the condition remain unclear.
• Both central and peripheral theories have been proposed.
• Likely multifactorial
Central Nervous System Theories
• Revolves around the concept of neuroplasticity and cortical
reorganization.
• Areas representing the amputated body part are taken over by
neighboring representational zones in both the somatosensory and
motor cortex
• Extent of remapping proportional to intensity of pain
Central Nervous System Theories
• Body schema theory postulated by Head and Holmes in 1912, later
expanded by Melzack and termed neuromatrix theory
• Involves the internal representation of spatial and biomechanical processes
reflecting in bodily experience
• Damage within any of the systems involved result in perceptual distortion
• Neuromatrix theory adds to this by including cognitive and emotional
factors.
• Neurosignature refers to the patterns of activity generated within the brain
that are continuously being updated based upon one’s conscious
awareness and perception of the body and self.
• Deprivation of various inputs from the limbs to the neuromatrix cause an
abnormal neurosignature to be produced
Peripheral Nervous System Theories
• Reinforced by correlation between residual limb pain and phantom pain
• Mechanism remains unclear, however, it is postulated phantom pain
may stem from neuromas formed at the site of amputation
• Neuromas may exhibit abnormal activity following mechanical or
chemical stimulation generating ectopic impulse discharge
• Ectopia may drive neuroplasticity and sensitization leading to increased
sympathetic tone that serves as a feedback loop to maintain phantom
pain
• Pain is not consistently abated with neuroma or nerve/plexus blocks
• Vaso et al. (2014) propose the dorsal root ganglia, which remain intact
after amputation may also be implicated in pain due to ectopia
Multifactorial Theory
• Ramachandran and Hirstein (1998) propose that there are at least 5
different sources that contribute to phantom pain:
1.
2.
3.
4.
5.
Residual limb neuromas
Cortical remapping
Corrollary discharge
Body image
Somatic memories
All 5 components may work together and reinforce each other
Treatment options
• Limited options without clear consensus on an optimal regimen
• Common pharmacological treatment includes opioids, anticonvulsants,
lidocaine/mexiletine, clonidine, ketamine, amitryptaline, NSAIDs, and
calcitonin.
• Opioids bind to central and peripheral receptors providing analgesia
without loss of touch, proprioception, or consciousness.
Pharmacological treatment
• Studies demonstrate opioids may diminish cortical reorganization
• Huse et al. (2001) small, double-blind crossover trial (n=12)
showing evidence of reduced cortical reorganization with
morphine leading to reduced pain.
• McCormick et al. (2014) reports the best evidence in the literature
for use of IV ketamine and IV morphine perioperatively and PO
morphine for long term treatment, 8 weeks to 1 year
• Level 2 evidence for gabapentin, both oral (PO) and intravenous
(IV) morphine, tramadol, intramuscular (IM) botulinum toxin, IV
and epidural Ketamine
• Level 3 evidence for amitriptyline, dextromethorphan, topiramate,
IV calcitonin, PO memantine, continuous perineural catheter
analgesia with ropivacaine
• Level 4 evidence for methadone, intrathecal (IT) buprenorphine, IT
and epidural fentanyl, duloxetine, fluoxetine, mirtazapine,
clonazepam, milnacipran, capsaicin, and pregabalin.
• Sympathetic targets and NSAIDS have not been well studied
TENS
• Katz and Melzack demonstrated significant pain relief in patients with the
use of transcutaneous electrical stimulation
• RCT (1991) demonstrated significant decrease in pain with auricular
TENS
• Carabelli and Kellerman (1985) showed pain relief with application of TENS
to unaffected side in 3 patients, no return of symptoms at 6 month follow up
• Finsen et al. (1988) performed a single–blinded trial (n=51) and found no
significant difference in post operative or chronic limb pain with the use of
TENS.
• Phantom pain after TENS was significantly lower between four months
and one year follow up
• Mulvey et al. (2012) performed a pilot study demonstrating reduction of
pain on movement and at rest in 10 subjects.
Implantable Stimulators
• Temporary and immediate relief found by deep brain stimulation of the ventral
caudal thalamic nucleus and posterior columns.
• Bittar et al. (2005) showed mean reduction of pain by 62% at one year follow up
for 3 patients
• Perreira and Boccard (2013) demonstrated efficacy in 5 amputee subjects at one
year.
• Spinal cord stimulation does not appear to help reliably decrease the intensity or
frequency of phantom pain.
• Largest study performed by Broggi et al in 1996 (n=26), with 58% success rate at
2 year follow up.
• With advances in spinal cord stimulators, recent literature is limited to case reports
regarding use in phantom limb pain
• Katayam et al. (2001) studied the effect of SCS, DBS, and MCS on 19 patients
with phantom pain
• Satisfactory long term pain control was achieved in 6 of 19 (32%) by SCS, 6 of
10 (60%) by DBS and 1 (20%) of 5 by MCS.
• No evidence of an advantage of MCS over SCS and DBS of the thalamus
Other modalities
• Acupuncuture has demonstrated mixed and inconsistent results.
• Other treatments reported to have mixed results include anesthetic and
surgical neuroablation as well as psychologic interventions
• Vaso et al. (2014) demonstrated spinal and intraforaminal block (n=31)
consistently attenuated, and often completely eliminated both phantom
pain and sensation in lower limb amputees
Mirror Therapy
• Ramachandran et al. proposed the use of mirrors in 1996
• Patient views the reflection of their intact limb moving in a mirror placed
strategically to mimic movement on the affected side
• Chan et al. (2007) performed a randomized, sham-controlled crossover
study showing significant decrease in pain for patients who underwent
mirror therapy in comparison to 2 control groups
•mental visualization was ineffective and may actually worsen pain
• Ramachandran poses that the mirror resolves the visual-proprioceptive
dissociation proposed as an explanation for phantom pain.
• Mechanism remains unclear
Mirror Therapy
• Rizollati et al. (2006) demonstrated the existence of “mirror neurons” in
macaques that fire both when the animal performs an action, as well as
when it observes the same action performed.
• Ramachandran et al. (2008) further demonstrated that touching the
virtual image in the mirror is sufficient to elicit tactile sensation in the
phantom limb
• Activation of mirror neurons modulates somatosensory inputs and may
block pain perception in the phantom limb.
Mirror Therapy
• Deconinck et al. (2014) performed a systematic review to asses the effect of mirror
therapy on brain activation during a motor task
• Mirror therapy increases neural activity in areas involved with allocation of attention and
cognitive control (dorsolateral prefrontal cortex, posterior cingulate cortex, S1 and S2,
precuneus).
• Evidence for ipsilateral projections from the contralateral M1 to the untrained/affected
hand as a consequence of training with mirrors
• Apart from activation in the superior temporal gyrus and premotor cortex, there is little
evidence it activates the mirror neuron system.
• Mirror therapy can exert a strong influence on the motor network, mainly through
increased cognitive penetration in action control.
• Variance in methodology and the lack of studies that shed light on the functional
connectivity between areas still limit insight into the actual underlying mechanisms
Conclusion
• Further research is needed to determine the relationship between
proposed mechanisms of phantom pain
• Treatment plan should be targeted to symptoms as well as underlying
mechanisms
Thank You
References
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