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Post-Amputation Pain
NSW Physiotherapists in Amputee
Rehabilitation 14 June 2013
Dr R. Craig Davenport
Rehabilitation Physician
Post-Amputation Pain
• Phantom Limb Pain
• Residual Limb Pain (Stump Pain)
• Phantom Sensations
Residual Limb (Stump) Pain
• More of an issue in immediate post-amputation period
• Descriptors:
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Sharp
Burning
Electrical-like
Skin-sensitive
Localised to a superficial incision, or deep pain, or
generalised in the residual limb
• Residual limb pain incidence may be as high as 74%
and can persist for many years
Phantom Sensations
• Defined as non-painful perceptions emanating from lost body part after deafferentation or amputation
• Common
▫ ~1/3 in first 24 hours
▫ ¾ at 4 days
▫ 90% within 6 months
• Doesn’t require amputation  Can occur with Spinal Cord Injury and Brachial
plexus avulsion
• Usually in hands and feet (large cortical representation)
• Not restricted to limbs, can occur in ear, teeth etc
Phantom Sensations
• Types of sensations:
▫ Kinetic – perceived movement of a body part
▫ Kinesthetic – size, shape, or position of body part
▫ Exteroceptive perceptions – touch, pressure, tingling, temperature, itch,
vibration
• Associated with Phantom Pain  phantom pain rare in those without
phantom sensations
• Often experience telescoping over time
Phantom Limb Pain
• Defined as an unpleasant sensation in
distribution of the lost or de-afferentated
body part
Phantom Limb Pain
• First described by 16th century French military surgeon Ambrose Pare
• The term “Phantom Limb Pain” coined by 19th century civil war surgeon
Silas Weir Mitchell
• Incidence of PLP common – between 40% and 80%
• Similar between civilian and military, and between different
aetiologies
• Not only in amputations, but also occurs in congenital limb deficiency
Risk Factors for Phantom Limb Pain
• Presence of pre-amputation pain severity
▫ Relationship to pre-amputation pain severity exists for first few
months, but probably not for pain >6 months post-op
Fig 1 Pre‐amputation pain ≥20 increases the risk of phantom pain ≥20 after 1 week and 3
months (on a VAS, 0–100).
Nikolajsen L , and S. Jensen T Br. J. Anaesth. 2001;87:107116
©2001 by Oxford University Press
Risk Factors for Phantom Limb Pain
• Residual limb pain severity correlates to PLP severity
• Upper Limb Amputations > Lower Limb Amputations
• Females > Males
• Time after amputation
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Onset of PLP has two peaks: within 1st month & a year after amputation
Typically occurs within first 6 months
Prevalence decreases over time
Like Phantom Sensations, up to 2/3 experience Telescoping over time
Phantom Limb Pain - Descriptors
• Pain description can change over time
▫ exteroceptive-like (knife-like, stabbing) in
proximal limb or more generalised
▫ proprioceptive-like (burning, squeezing)
localised to distal areas of amputated limb
PLP descriptors
• Most common:
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Tingling
Throbbing
Piercing
Pins and needles
• Others:
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Sharp
Shooting
Electrical-like
Dull
Squeezing
Cramping
Factors influencing pain
• Stress/anxiety/depression/emotional triggers
contribute to persistence or exacerbation of
PLP
• Presence of depression associated with
characterisation of more severe pain
• Possible genetic predisposition to development
of neuropathic pain
Mechanisms of Phantom Pain
• Peripheral
• Central
▫ Spinal
▫ Supra-spinal (Brain & Brainstem)
Mechanisms of PLP
• Peripheral
▫ Tissue injury
▫ neural injury
▫ de-afferentation
▫ Proximal portion of nerve sprouts to form Neuroma 
upregulation of voltage-gated sodium channels, downregulation of K-channels. Development of ephapses (nonfunctional connections between neurons)  hyper-excitability
and increased spontaneous discharge
▫ Chemosensitivity to circulating catecholamines (eg adrenalin)
 pain increased with stress
Spinal Cord – Dorsal Horn changes
• Axonal sprouts form connections with neurons in receptive field
• Loss of afferent input causes reduced descending inhibitory input from
reticular formation in brainstem
• Central sensitisation
▫ Expansion of neuronal receptive field, hyper-excitability
▫ Increased NMDA receptor activity – mediated by Substance P, tachykinins,
neurokinins at dorsal horn
▫ “Wind-up” – up-regulation of receptors in the area
▫ Loss of target neurons for descending inhibitory pathways
▫ Spinal disinhibition due to loss of local inhibitory intersegmental spinal interneurons
• But
▫ spinal ablative treatments (cordotomy tractotomy etc) often fail to give long term relief
Brain Changes – The Homunculus
Brain changes
• Cortical re-organisation in primary somatosensory and motor cortex
▫ Extent of re-organisation related to degree of pain and size of deafferented region
• Body-schema – Neuromatrix and Neurosignature – loss of input
causes abnormal neurosignature to develop
• Incongruence of motor intention and sensory feedback –
involves parietal and frontal lobes involved
fMRI in PLP and non-PLP subjects
Psychogenic mechanisms
• Not well supported by evidence
• previously thought to be associated with
passive coping styles and catastrophising
behaviour traits
Pain Limbic Connections
What Causes might be identified and possibly treated?
Residual Limb Pain - Causes
• Post-surgical nocipceptive tissue trauma pain
• Neurogenic causes- clinically significant neuroma
• Prosthogenic causes
▫ Poor fitting socket
 Too tight/lack of distal contact, insufficient bony relief,
 Too loose, excessive end-bearing, pistoning
▫ Socket malalignment with torque forces in weight-bearing
▫ Incorrect donning of prosthesis
▫ Incorrect use of socks
• Adherent Scar tissue
• Heterotopic ossification – initially acute inflammatory pain and
then pressure effects
Residual Limb Pain - Causes
• Arthrogenic – eg OA of knee
• Ischaemic – ongoing poor vascular supply
• Sympathetically-maintained – eg Complex Regional Pain Syndrome
• Referred from spine eg Radicular/Facet Joint/SI Joint pain generator
• Stump or wound Infection
• Pain from associated injuries
• Pain from co-morbidities
• Musculoskeletal Pain from Gait abnormalities
How to tell……
• Referred from facet joint/ SI joint/ radiculopathy
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diagnostic blocks may help
• Ischaemia
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transcutaneous oxygen tension <20mmHg
• Neuroma
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Palpation point neuropathic pain, Ultrasound/MRI
• Prosthesis-related pain
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pain on weight bearing, or after prolonged wearing, skin or soft tissue changes
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may prompt socket adjustments which may relieve pain
• Stump infections – soft-tissue or bone
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blood tests/ultrasound/MRI/Nuclear imaging studies
• Bone spurs
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palpation and plain radiographs
Treatment
Treatment Approaches
• Few controlled trials to guide treatment
• Often extrapolation of treatments for neuropathic pain
• Multidisciplinary and Multi-modal Approach most successful
• Multimodal approach
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Injections
Pharmacotherapies
Physical therapies
Psychological therapies
Complimentary and alternative therapies
Surgery
Preventative Measures
Pharmacologic therapies
• Common oral medications:
▫ Simple Analgesics – Paracetamol & NSAIDs
▫ Opioids – some evidence for morphine and tramadol
 Effective for PLP, possibly reduces cortical re-organisation
 Better when combined with other agents
▫ Anti-depressants
 Tricyclic antidepressants/Serotonin Re-uptake inhibitors, Sodium
channel blockade, NMDA antagonist effects - mixed results for PLP
 Mirtazepine
 Duloxetine
▫ Anti-convulsants
 Gabapentin – mixed results
 Carbamazepine
 Pregabalin (Lyrica)
Pharmacologic therapies - uncommon
• Calcitonin – mixed results, mechanism of effect unclear – not used
• NMDA receptor antagonists – blocks cascade leading to
sensitisation of Wide Dynamic Range neurons in spinal cord
▫ Ketamine – short follow-up periods, psychogenic side effects
▫ Dextromethorphan – not used routinely
▫ Memantine – mixed results in RCTs – not used
• Others
▫ Sodium channel blockers – lignocaine/mexiletine – not effective
▫ B-blocker - Propranolol
▫ Ca-channel blocker - Nifedipine
Injection Therapies
• More useful for residual limb pain than phantom limb pain
▫ ? Due to greater contribution of peripheral mechanisms in RLP compared with PLP
• Regional nerve blocks (anaesthetics/corticosteroids) – often not long-lasting
• Botulinum toxin A perineural blocks – currently under study, not enough evidence yet
• Pulsed Radiofrequency – small study
• TNFα inhibitor (etanercept) perineural injection– small study
• Sympathetic nerve blocks – small study
• Ambulatory Continuous Peripheral nerve block for 6 days – small cross-over study –
promising long term improvements in 2/3 subjects
Prosthetic Approaches
• Prosthetist review, adjustment of socket fit
• Alignment changes
• Replacement socket if stump volume change, weight change
etc
• Utilise different prosthetic componentry eg. silicon/urethane
liners, shock absorbers, torsion adaptors, multi-axial ankles
• Shift weight bearing away from stump: thigh-lacers, ischial
bearing prostheses – much less common since Silicon
available
Non-Pharm Treatments
• Psychological interventions – aim to facilitate adaptation to
pain, body image, negative emotions
• EBM limited for these approaches
• Cognitive Behavioural Therapy – no RCTs; RCT combining CBT and
mirror therapy in progress
• Hypnosis – small RCT showed benefit, 3 sessions
• Guided imagery – anecdotal
• Biofeedback – anecdotal
• Relaxation Techniques
Mirror Therapy
Mirror neurons in the brain – fire
when perform movement or when
observe movement
Activation may modulate
somatosensory inputs and block
protopathic pain perception in
phantom limb i.e. lessens effect of deafferentation
RCTs one +ve, one –ve
Recent study added illusory touch
stimulation for cases where
movement caused increased pain
(Schmalzl et al 2013)
Mirror therapy – influencing cortical re-organisation
Reduction of PLP with fMRI evidence of reduction in re-organisation
Non-Pharm Treatments
• Acupuncture – No RCTs, only descriptive
studies
• TENS – shown to be helpful
▫ ?Contralateral limb
▫ Low-Freq, hi intensity
• Laser
• Ultrasound/Heat – musculoskeletal pain
Non-Pharm Treatments
• Successful rehabilitation may reduce the amount of
pain
• Stump massage and familiarisation/desensitisation
• Early prosthetic use
▫ In upper extremity amputees, phantom pain was
decreased by the use of a prosthesis which allowed
extensive use of the affected limb but not with cosmetic
prosthesis use
• Oedema control/Use of stump shrinker/RRD
Early weight-bearing??
• No consensus on the impact of weight bearing on early wound healing
• Possible benefits for reducing oedema and stimulation of circulation, reducing cortical reorganistaion
• Possible detrimental effects of excessive loading damaging fragile new tissue and harming
the healing response
• Still no standard protocols for the amount, time, and advancement of weight bearing
• Published studies use many different weight-bearing protocols
• Main concern will be for poorly vascularised limbs or friable skin
• My approach… anytime after 1 week if the tissues look good, but logistics mean that
rarely less than 2-3 weeks post-op, otherwise after clips out and suture line healed in
questionable stumps
Surgical Intervention
• Stump Revision occasionally useful for difficult to fit stumps
• Clinically significant neuromas may require resection if prosthetic changes not sufficient mixed results with excision
• Excision of Heterotopic bone and bone spurs – may recur
• Neurosurgical procedures:
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DREZ lesioning
Spinal Cord Stimulation – evidence for PAP less robust than for other neuropathic pain states
Peripheral Nerve Stimulation – might work if one or two nerve territories affected, may not
work if spinal or cortical re-organisation
Deep Brain Stimulation – PVG, thalamic nuclei, motor cortex – case series evidence – mixed
results for PAP
• Electroconvulsive therapy
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A case report
Spinal Cord Stimulator
Surgical Intervention
• Stump Revision occasionally useful for difficult to fit stumps
• Clinically significant neuromas may require resection if prosthetic changes not sufficient mixed results with excision
• Excision of Heterotopic bone and bone spurs – may recur
• Neurosurgical procedures:
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DREZ lesioning
Spinal Cord Stimulation – evidence for PAP less robust than for other neuropathic pain states
Peripheral Nerve Stimulation – might work if one or two nerve territories affected, may not
work if spinal or cortical re-organisation
Deep Brain Stimulation – PVG, thalamic nuclei, motor cortex – case series evidence – mixed
results for PAP
• Electroconvulsive therapy
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A case report
Deep Brain Stimulation
Surgical Intervention
• Stump Revision occasionally useful for difficult to fit stumps
• Clinically significant neuromas may require resection if prosthetic changes not sufficient mixed results with excision
• Excision of Heterotopic bone and bone spurs – may recur
• Neurosurgical procedures:
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DREZ lesioning
Spinal Cord Stimulation – evidence for PAP less robust than for other neuropathic pain states
Peripheral Nerve Stimulation – might work if one or two nerve territories affected, may not
work if spinal or cortical re-organisation
Deep Brain Stimulation – PVG, thalamic nuclei, motor cortex – case series evidence – mixed
results for PAP
• Electroconvulsive therapy
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A case report
Preventative Treatments
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Pre-emptive analgesia/anaesthesia
▫ Pre-op, intra-op, early post-op period (<2 weeks) – goal to avoid long term spinal sensitisation
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Still no definitive evidence
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Prevention of Acute PLP
▫ Epidural treatments – 3 trials – mixed results, best quality study no benefit
▫ Regional nerve blocks – 3 studies – no effect
▫ IV calcitonin – 1 study – no benefit
▫ TENS – 1 study, no benefit
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Prevention of chronic PLP
▫ Pre-op epidural anaesthesia – studies mixed but may suggest need to be started at least 24 hours
pre-op
 May not need epidural Rx, other forms of good pre-op pain control may be equivalent
▫ Perineural anaesthesia – mixed results
▫ Prophylactic gabapentin from D1-30 not shown to prevent PLP
▫ TENS – RCT showed lower incidence at 4 months but no benefit at 4 weeks and 1 year, but
improved wound healing time and lower re-amputation rate
▫ Mirror therapy prophylactically – small case series showed promise
Cochrane Review 2012 – Pharmacologic
Interventions for PLP
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Morphine - Short-term effect for pain relief
Ketamine – analgesic effects
Gabapentin – trend towards pain relief
Amitriptyline – not effective for PLP
Memantine – not effective
Calcitonin – variable findings
• i.e. NOT MUCH HELP
Thankyou