FRCA Notes

Post-Amputation Pain Syndromes

Phantom limb pain appeared as an SAQ in 2019 (53% pass rate), with examiners 'surprised at the lack of knowledge' of clinical features and management.

It re-emerged as a CRQ in 2022 (47% pass rate), with similar failings as in 2019.

Resources

  • Post-amputation pain syndromes continue to pose a challenge, especially with a lack of a clearly understood pathophysiological mechanism
  • The magnitude of tissue injury and multi-focal sites of pain generation are responsible for the degree of pain post-operatively
  • They are associated with the highest rate of chronic post-surgical pain of any surgery

Acute stump pain

  • Immediate, nociceptive pain localised to the site of amputation
  • Is a direct manifestation of tissue trauma involved in stump formation

Chronic/persistent stump pain

  • Is a largely nociceptive ± neuropathic pain persisting in the operative stump for >2-3months post-operatively
  • Affects a small minority (approximately 10%) of patients, with prolonged pain perceived as arising from the stump
  • The causative factor is variable, but may include:
    • Bony spurs
    • Heterotrophic ossification (63% of those with traumatic amputation)
    • Arterial insufficiency
    • Neuromas
    • Haematomas
    • Sinister pathology including superficial or deep tissue infection

Phantom limb sensation

  • Non-painful sensory experiences perceived to be originating from the absent limb itself
  • It a near-universal experience in the early post-operative phase

Phantom limb pain

  • The perception of noxious stimulus from the missing body part, which is often distressing for the patient

  • Prevalence is as high as 80%
    • 92% of those who experience phantom limb pain have onset of pain within the first week post-operatively
    • Occurs in 22-64% of post-mastectomy patients

  • Described as an intermittent, burning/electrical-type pain lasting minutes-to-hours in the distal aspect of the amputated limb
  • In a minority of patients, often those with ischaemic vascular disease, it may instead take the form of a constant unremitting pain

Other

  • Chronic back pain due to altered gait mechanics

Peripheral mechanisms

  • Soft-tissue trauma results in inflammation, disruption of normal neurological pathways and deafferentation
  • This encourages sprouting of neuromas from the proximal, damaged portion of Aδ and C-fibres
  • Neuromas possess reduced activation thresholds owing to a relatively increased density of sodium channels
    • This increases incidence of ectopic potentials and spontaneous discharges of afferent neurones
    • May manifest has persistent stump pain, phantom limb sensation or phantom limb pain
  • There may be spontaneous discharge in the DRG
  • There may be coupling to the sympathetic nervous system

Spinal cord mechanisms

  • The main theory of spinal cord-derived phantom limb pain is central sensitisation in the dorsal horn

  • Post-amputation inflammation induces neurones not normally responsible for nociceptive transmission to grow into lamina II of the dorsal horn
  • This increases the neuronal receptive field and NMDA-receptor activity in the dorsal horn

  • There is 'wind-up' phenomenon; an increased susceptibility to activation by stimuli such as substance P, tachykinins and neurokinins
  • There is concurrent restructuring of:
    • C-fibres in Rexed's laminae
    • Descending inhibitory pathways, resulting in spinal disinhibition
  • This process culminates in regional hypersensitisation of the neuronal field representing the amputated limb

Central (brain) mechanisms

  • Two proposed mechanisms include:
  1. Cortical reorganisation
    • Neuroplasticity leads to areas of the cortex representing the amputated region being taken over by neighbouring primary somatosensory or primary motor cortical regions
    • Explains why stimulation of nerves around the amputation site results in a phantom sensation
    • The degree of cortical re-organisation correlates with the severity of symptoms
    • E.g. full bladder may cause phantom limb pain due to reorganised cortex

  2. Disturbance of the neuromatrix/neurosignature
    • Amputation eliminates input into a collection of neurons which integrate transmission from somatosensory, limbic, visual and thalamocortical components ('the neuromatrix')
    • This distorts the central cortical representation of the self ('the neurosignature') and leads to generation of a phantom sensation


Risk factors for phantom limb pain
Pre-amputation pain, especially if severe
Presence of stump pain
Bilateral amputations
Lower limb amputation
Repeated limb surgery
Increasing age
  • The presence of pre-operative pain regardless of its anatomical relationship to the surgical site significantly increases the risk of developing post-operative chronic pain
  • There may be a heritability (30-70%) and genetic components (GCH1 and KCNS1 genes) which increase the vulnerability of patient to acute- and chronic-pain syndromes

Non-pharmacological therapies

  • Graded motor imagery is effective in reducing phantom limb pain severity
  • Virtual reality technology reduces phantom limb pain severity
  • TENS
  • Pain management programme

Simple analgesia

  • Paracetamol and (if appropriate) NSAIDs should be incorporated into the analgesic regimen for post-amputation pain
  • They benefit patients with acute stump pain
  • There is no evidence for an impact on the incidence/severity of chronic stump or phantom limb pain

Opioid analgesia

  • Opioid analgesia is a mainstay for acute stump pain, with level 1 evidence supporting use of PCA's in the immediate post-operative period
    • No evidence supports one opioid being superior to any other
    • Opioid PCA use (started 48hrs pre-op. until 48hrs post-op.) decreases the incidence and severity of phantom limb pain at 6 and 12 months post-operatively

  • Opioids are also effective for the nociceptive nature of chronic stump pain
    • May reduce the degree of cortical reorganisation associated with pain intensity
    • Tramadol is particularly effective; tapentadol may be equally so

Regional anaesthesia

  • Level 1 evidence supporting use of epidural or perineural catheters in reducing acute post-operatively pain when continued for 72hrs post-operatively
    • Both have opioid-sparing effects
    • Regional anaesthesia is the gold standard for management of acute post-operative pain

  • Epidural analgesia, as part of a multimodal regimen, reduces the incidence & severity of phantom limb pain at 12 months post-operatively when continued for 48hrs post-operatively
  • Some evidence that peripheral nerve blocks may prevent phantom limb pain

NMDA receptor antagonists

  • Ketamine (and dextromethorphan) are useful in the management of acute post-amputation pain
    • E.g. ketamine infusion (0.1-0.2mg/kg/hr) in the setting of pain refractory of opioid monotherapy, or where monotherapy is limited by opioid-induced side-effects
    • PO ketamine may be used for refractory limb pain

  • At best weak evidence for IV ketamine in the treatment of chronic stump pain or phantom limb pain
  • Insufficient literature to support use for long-term prevention of phantom limb pain

Lidocaine

  • Limited evidence to suggest lidocaine infusions may decrease the severity of acute stump pain
  • Overall unconvincing evidence that lidocaine improves post-amputation pain, despite its use for other localised neuropathic pain

Clonidine

  • Perineural clonidine reduces mechanical hypersensitivity after (generic) nerve injury, but no evidence examining its use as an adjuvant to perineural blockade in amputation

Anti-depressants

  • No convincing evidence of efficacy of TCA's in acute stump pain or phantom limb pain
  • They often merely cause drug interactions and side-effects

Gabapentinoids

  • Evidence for use in acute stump pain, with an opioid sparing effect
  • Early post-operative use does not reduce the incidence of chronic stump pain or phantom limb pain
  • Level 2 evidence that gabapentinoids reduce pain severity in establish phantom limb pain, but not functionality
  • Dosing regimens:
    • Gabapentin 100mg TDS up-titrated to a maximum 1200mg TDS
    • Pregabalin 25-75mg OD up-titrated to a maximum 300mg BD

Salmon calcitonin

  • Unclear mechanism of action, possibly via direct inhibition of neurons in the central serotonergic pathways responding to peripheral stimulation
  • No significant evidence it prevents phantom limb pain
  • Mixed evidence for its efficacy in treating established phantom limb pain
    • 200IU given subcutaneously once daily (IV is associated with higher risk of side-effects such as nausea and vomiting)

Novel therapies

  • Botulinum toxin A causes chemodenervation of distal nerve segments and reduces chronic stump pain
  • Pulse radiofrequency ablation of neuromas reduces chronic neuropathic pain in those with symptomatic neuromas

Perioperative analgesic management


  • Patient education
  • Optimise mental health
  • Acute pain service review
  • Consider 24hrs pre-operative epidural or regional infusion analgesia

  • Pre-incision regional analgesia e.g. spinal, epidural or regional block/catheter
  • Intra-operative ketamine infusion
  • Paracetamol and NSAID (unless contraindicated)
  • Systemic opioids
  • ± IV magnesium
  • ± IV clonidine

  • Regular paracetamol and NSAID
  • Regional anaesthetic infusion for 72hrs if possible
  • IV ketamine infusion for 24hrs post-operatively
  • Systemic opioids e.g. PCA

  • MDT reviews:
    • Acute pain service
    • Psychological support
    • Therapy services