1. Post-Amputation Pain Dr R. Craig Davenport
NSW Physiotherapists in Amputee Rehabilitation 14 June 2013
Dr R. Craig Davenport
Rehabilitation Physician

2. Post-Amputation Pain Phantom Limb Pain Residual Limb Pain (Stump Pain)
Phantom Sensations

3. Residual Limb (Stump) Pain
More of an issue in immediate post-amputation period
Descriptors:
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

4. Phantom Sensations
Defined as non-painful perceptions emanating from lost body part after de- afferentation 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

5. 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

6. Phantom Limb Pain
Defined as an unpleasant sensation in distribution of the lost or de-afferentated body part

7. 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

8. 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

9. Fig 1 Pre‐amputation pain ≥20 increases the risk of phantom pain ≥20 after 1 week and 3 months (on a VAS, 0–100).
Fig 1 Pre‐amputation pain ≥20 increases the risk of phantom pain ≥20 after 1 week and 3 months (on a VAS, 0–100). Data from the 1 week interview are shown. Each dot represents one patient, n=54. P=0.04, Fishers’ exact test. (From Nikolajsen and colleagues 1997, with permission).
Nikolajsen L , and S. Jensen T Br. J. Anaesth. 2001;87:
©2001 by Oxford University Press

10. 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
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

11. 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

12. PLP descriptors Most common: Others: Tingling Throbbing Piercing
Pins and needles
Others:
Sharp
Shooting
Electrical-like
Dull
Squeezing
Cramping

13. 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

14. Mechanisms of Phantom Pain
Peripheral
Central
Spinal
Supra-spinal (Brain & Brainstem)

15. Mechanisms of PLP Peripheral Tissue injury neural injury
de-afferentation
Proximal portion of nerve sprouts to form Neuroma  upregulation of voltage-gated sodium channels, down- regulation of K-channels. Development of ephapses (non- functional connections between neurons)  hyper-excitability and increased spontaneous discharge
Chemosensitivity to circulating catecholamines (eg adrenalin)  pain increased with stress

16. 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 inter- neurons
But
spinal ablative treatments (cordotomy tractotomy etc) often fail to give long term relief

17. Brain Changes – The Homunculus

18. Brain changes
Cortical re-organisation in primary somatosensory and motor cortex
Extent of re-organisation related to degree of pain and size of de- afferented 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

19. fMRI in PLP and non-PLP subjects

20. Psychogenic mechanisms
Not well supported by evidence
previously thought to be associated with passive coping styles and catastrophising behaviour traits

21. Pain Limbic Connections

22. Phantom Pain often triggered by Residual Limb Pain
What Causes might be identified and possibly treated?

23. 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

24. 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

25. How to tell…… Referred from facet joint/ SI joint/ radiculopathy
diagnostic blocks may help
Ischaemia
transcutaneous oxygen tension <20mmHg
Neuroma
Palpation point neuropathic pain, Ultrasound/MRI
Prosthesis-related pain
pain on weight bearing, or after prolonged wearing, skin or soft tissue changes
may prompt socket adjustments which may relieve pain
Stump infections – soft-tissue or bone
blood tests/ultrasound/MRI/Nuclear imaging studies
Bone spurs
palpation and plain radiographs

26. Treatment

27. Treatment Approaches Few controlled trials to guide treatment
Often extrapolation of treatments for neuropathic pain
Multidisciplinary and Multi-modal Approach most successful
Multimodal approach
Injections
Pharmacotherapies
Physical therapies
Psychological therapies
Complimentary and alternative therapies
Surgery
Preventative Measures

28. 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)

29. 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

30. 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

31. 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

32. 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

33. 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 de- afferentation
RCTs one +ve, one –ve
Recent study added illusory touch stimulation for cases where movement caused increased pain (Schmalzl et al 2013)

34. Mirror therapy – influencing cortical re-organisation Reduction of PLP with fMRI evidence of reduction in re-organisation

35. 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

36. 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

37. 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 re- organistaion
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

38. 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:
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
A case report

39. Spinal Cord Stimulator

40. 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:
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
A case report

41. Deep Brain Stimulation

42. 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:
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
A case report

43. Preventative Treatments
Pre-emptive analgesia/anaesthesia
Pre-op, intra-op, early post-op period (<2 weeks) – goal to avoid long term spinal sensitisation
Still no definitive evidence
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
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

44. Cochrane Review 2012 – Pharmacologic Interventions for PLP
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

45. Thankyou