1. Phantom Limb Pain: Current Theories and Evidence Based Treatments
Christopher V Boudakian, DO PGY-4
Rusk Rehabilitation
NYU Langone Medical Center

2. 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

3. 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

4. 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

5. 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

6. 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.

7. Characteristics of phantom pain
Often described as burning, cramping, electrical shocks, severe itching, or stabbing
Episodes may last seconds to hours.

8. 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

9. 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

10. 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

11. 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

12. Multifactorial Theory
Ramachandran and Hirstein (1998) propose that there are at least 5 different sources that contribute to phantom pain:
Residual limb neuromas
Cortical remapping
Corrollary discharge
Body image
Somatic memories
All 5 components may work together and reinforce each other

13. 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.

14. 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

15. 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.

16. 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

17. 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

18. 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

20. 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.

21. 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

22. 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

23. Thank You

24. References
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Vaso et al. “Peripheral nervous system origin of phantom limb pain” Pain 21 April 2014; Epub ahead of print
Uustal, H., et al. “Pain Issues and Treatment of the Person with an Amputation” Phys Med Rehabil Clin N Am 25 (2014) 45–52
McCormick et al. “Phantom limb pain: A Systematic Neuroanatomical-Based Review of Pharmacoloigcal Treatment” Pain Medicine 2014; 15: 292–305
Nikolaijsen, L., et al. “The influence of preamputation pain on postampuation stump and phantom pain” Pain 1997; 72: 393–405
Melzack R. “Prolonged relief of pain by brief, intense transcutaneous somatic stimulation.” Pain. 1975;1:357–373.
Carabelli R, Kellerman W. “Phantom limb pain: relief by application of TENS to contralateral extremity” Arch Phys Med Rehabil Jul;66(7):466-7
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