Epidemiology
Post amputation chronic pain in 30-50% of patients. Disabling in 5-10%
Pathophysiology
Pain after amputation involves nociceptive pain due to bone and soft tissue injury, and neuropathic pain from direct neural trauma and central sensitisation
Distal end of afferent fibres undergo retrograde degeneration with subsequent regenerative sprouting
Damaged A and C fibres form neuromas with increased ectopic firing and abnormal response to chemical and mechanical stimuli
Upregulation of sodium channels lowering stimulation threshold
Increased ectopic discharges leads to increased excitatory input at the DRG and apoptosis of inhibitory interneurons
Sympathetic nervous system up regulation with catecholamine sensitisation possibly
Reorganisation of signal processing in the spinal cord with Adelta and beta fibres sprouting into lamina 2. Phenotypic switching can also lead to Abeta fibres releasing nociceptive peptides
Activation of microglia leads to neurotrophic factors released further inhibiting interneurons and increasing release of excitatory neurotransmitters
Cortical reorganisation - remarrying to areas adjacent to and distant from the somatosensory area
Psychological factors also modulate descending inhibitory processes
Pain is often complicated by polypharmacy and severe premorbid co-morbidity in patients undergoing amputation
Acute pain:
Stump pain
- Sharp, aching and severe.
- Primarily nociceptive due to extensive tissue trauma
- Neural injury also leads to a significant neuropathic component.
- Baseline treatments include: opioids and ketamine
- Acute stump pain expected to resolve within a few weeks but up to 10% (or higher) end up with persistent stump pain
Other causes of worsening acute pain to consider include: Infection, wound breakdown, arterial insufficiency, osteomyelitis, bone spur, haematoma, insufficient myoplasty covering, or poorly fitting prosthesis.
Persistent pain:
Chronic pain occurs in up to 95% of amputees!
Stump ischaemia
Can be difficult to diagnose by examination alone, but transcutaneous oxygen tension less than 20 mmHg at the level of the stump - can be indicative
Infection
- Rates are high after amputation (amount of tissue injury and comorbidities)
- Infection more common below knee > above knee - in diabetic patients, patients with poor nutritional status, vascular compromise, or if preexisting infection within the limb. Infection must be treated early and aggressively.
Stump neuroma:
- Nerve is severed --> intense immune-cell mediated inflammatory reaction
- Causes pain and peripheral sensitisation
- Initiates free endings of unmyelinated A-delta and C-fibres to sprout forming a tangled end at the cut surface of the nerve bundle
- Alters sodium channel function --> reduced activation potentials leading to spontaneous firing
- This triggers unprovoked pain and contact sensitivity in the neuroma region
- Often associated with phantom limb pain
- Take months to form - focal pain with local sensory changes
Pressure points
Can be identified commonly with a plain radiograph of the stump
Depends on where the stitching of the fascia has occurred - can give an indication of where pressure points can be created
The distal end of the bone is cut at an angle and this can be assessed on a plain radiograph
Heterotopic ossification:
Rarely considered as a cause for persistent stump pain
- Involves calcium deposition in the soft tissues of the stump
- Found in up to 63% of traumatic amputees
- Maybe bisphosphonates help but good evidence is lacking
- NSAIDs could be helpful --> but are usually contraindicated in this group
- COX2 may be safer but there is no evidence
- Investigation is by simple Xray of the stump
DVT
Always consider
Phantom limb pain
Epidemiology:
Varies from 50-85% of amputees (depending upon the criteria)
Significantly affects the quality of life in 25-50% of patients
Risk factors:
Depression is NOT linked as a risk factor for the development of PLP, but it can become a secondary contributory problem.
Passive coping strategies and catastrophisation however have been linked with an increased risk of the development of PLP.
Possibly rigid thinking is also a problem - though none of these risk factors is clearly consistent in studies.
Inadequate pre and postoperative pain may increase the risk
Preemptive epidural anaesthesia may reduce the incidence and severity of phantom pain
Presentation:
Onset usually occurs soon after surgery but can be delayed
Patients can describe the limb in vivid detail - often in a distorted or abnormal position
Often the phantom pain fades with time - usually the first 6 months - but not always
Constant, unpleasant, dysaesthetic pain exacerbated by movement or stimulation of the affected cutaneous regions.
Sharp, shooting neuritic pain may be superimposed on these constant symptoms.
The sensation often last seconds to minutes, but can last for hours or even become permanent
Often limbs undergo a 'telescoping' phenomenon
Examination of the stump for complications is important considering neuromas, tumours, infection.
Pathophysiology:
Likel multifactorial with somatic, psychological, and social factors.
Peripherally, regenerative processes such as nerve resprouting with creating of a neuroma and/or altered peripheral signalling such as increased sodium channels and higher activity of C fibres. Also there can be spontaneous firing of DRG neurons.
Spinal cord changes, with both an increase in excitatory neurotransmitters such as glutamate and the NMDA system. There is believed loss of inhibitory interneuron activity.
Centrally, neuronal changes also occur such as cortical reorganisation. There is blurring of the boundaries between the previous limb representation, and surrounding areas. This may lead to triggering of sensation for the regions of the cortex previously mapping the limb, by other sensory inputs. This is termed an expansion of the neuronal receptive field. Therapies addressing these cortical changes (such as prosthetic wearing and/or mirror therapy) can significantly reduce these cortical changes, or even reverse them.
Treatment:
Treatment involves reassurance to patients that this sensation is normal after the loss of a limb and that the sensations are real not imagined!
Acute PLP:
Preoperative gabapentinoids have been tried to prevent the creation of PLP however there is minimal evidence
Ketamine perioperatively has not been shown to reduce acute postoperative pain nor the incidence of phantom limb pain at 6 mo. Lidocaine infusion has also been considered. However another trial did suggest improvement in chronic PLP.
Memantine was not superior to placebo. Botox was unhelpful. Dextromethorphan may have a small short term effect.
Calcitonin was not shown to offer benefit in PLP over placebo. Maybe some benefit in acute setting < 7 days.
Capsaicin was shown in a small study to be helpful with reduced PLP of 30-70% within the second to 7th week in a 12 week follow up. But after 7 weeks they returned somewhat to baseline.
Chronic PLP:
Therapies have been trialled to reduce the incidence/severity - including nonpharmacological (mirror box, virtual reality, peripheral nerve stimulation) and pharmacological (gabapentin (administer early), carbamazeine (if gabapentin does not work) memantine, ketamine, amitriptyline, lidocaine)
Nerve blockade particularly of the sympathetic nerves subserving the painful area can be considered. Exact mechanism of benefit is unknown. Neurodestructive therapies have poor or no benefit.
Opioids frequently do more harm than good.
Ice packs to the stump can help some patients. TENS can be tried. Spinal cord stimulation can be considered. Topical capsaicin can also be trialled though burning pain often makes this less helpful.
Sensory feedback from a prosthetic may also help - this is being explored. Sensory discrimination training puts several electrodes over the stump and the patient has to describe which are being fired at what times. It is suggested the same could be done with things like cotton swabs. They were doing 90mins/day over 2 weeks.
Flexion contracture
Can occur at the hip or knee and occur in 3-5% of amputations
Hip contractures >25 degrees leads to compensatory lumbar lordosis
More common in elderly and post stroke
Once it develops, it is VERY hard to correct
Preventative measures such as a rigid removable dressing is applied inraoperatively and kept postoperatively to straighten the knee
Risk factors (Srivastava, 2017).
Genetics: Chronic pain has a heritability ranging from 30% to 70%
Female gender and younger age are more likely to experience post operative pain GENERALLY
Psychological conditions: anxiety, depression, catastrophizing, illness perception, poor coping strategy, low sense of control, poor social control, poor social support and high expectations
The degree of pre-operative anxiety was correlated with the intensity of phantom limb pain in the post-operative period
Depressive symptoms were a significant predictor of level of pain intensity and bothersomeness after amputation long term.
Pain disease states: Fibromyalgia, migraine, IBS, irritable bladder and raynauds - all have an association with chronic post surgical pain
Pre-surgical pain: pre-operative pain generally, doesn't matter where, significantly increases risk of developing surgically induced chronic neuropathic pain or chronic post surgical pain Association with chronic post amputation pain however is more complex - evidence is not always consistent
Interoperative pain:
- Surgical technique with nerve injury is a risk factor for CPSP
- MAAAYBE - If adequate analgesia is not provided both intra- and post-operatively, the central nervous system continues to receive continuous nociceptive input from the periphery due to either sensitization of neurons, ectopic activity or phenotypic switch.This highlights the necessity of efficacious intra-operative analgesia.
Postoperative pain:
- High levels of pain in the acute post-operative period can predict CPSP.
- Type of surgery is less important (e.g. hernia, breast, thoracic and cholecystectomy)
- For CPAP specifically, evidence to demonstrate relation between efficacy of post-operative pain relief and prevention of CPAP is mixed
- Issues such as the duration of high-quality post-operative analgesia that is needed to prevent CPSP/CPAP are at present unaddressed.
References / Articles / Resources
Srivastava D. (2017). Chronic post-amputation pain: peri-operative management - Review. British journal of pain, 11(4), 192–202. https://doi.org/10.1177/2049463717736492
MJE Neil, FRCA FFPMRCA, Pain after amputation, BJA Education, Volume 16, Issue 3, March 2016, Pages 107–112, https://doi.org/10.1093/bjaed/mkv028 (https://academic.oup.com/bjaed/article/16/3/107/2389863)
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