Post-amputation Pain

Stephan A. Schug; Gail Gillespie

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Fitridge R, Thompson M, editors. Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists [Internet]. Adelaide (AU): University of Adelaide Press; 2011.

Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists [Internet].

Show details

Contents

< Prev Next >

21Post-amputation Pain

Stephan A. Schug and Gail Gillespie.

Author Information and Affiliations

Introduction

The phenomenon of pain in a missing limb has puzzled patients, doctors and the lay public for centuries. In the 16th Century the French military surgeon Ambroise Paré published a medical description of the enigmatic affliction, while in the 17th century the great philosopher Rene Descartes looked at its potential pathophysiology. The most famous ‘first’ description of the condition is attributed to the great neurologist Charles Bell,¹ but it was only in the later part of 19th Century, that the US military surgeon Silas Weir Mitchell introduced the term ‘phantom limb’: ‘There is something almost tragical, something ghastly, in the notion of these thousands of spirit limbs, haunting as many good soldiers, and every now and then tormenting them. . .’

We now know that post-amputation syndromes can occur with any amputated body part apart from limbs e.g. breast, tongue, teeth, genitalia and even inner organs such as the rectum.²^-⁴

Classification and Incidence of Post- Amputation Pain Syndromes

Following amputation (or deafferentiation injury such as brachial plexus avulsion) a number of phenomena can develop, which require differentiation.

Stump Pain

Stump pain is pain localized to the site of amputation. Stump pain can be acute (usually nociceptive) or chronic (usually neuropathic). Stump pain is most common in the immediate post-operative period.⁵ The overall incidence of chronic stump pain is in the range of 45%.⁶ The incidence of early stump pain is increased by the presence of severe preamputation pain⁷ and severe acute stump pain.⁸ The cause is unclear but probably multifactorial. Stump pain is problematic and can interfere with prosthesis use.

Phantom Sensation

Phantom sensation is defined as any sensory perception of the missing body part with the exclusion of pain. Almost all patients who have undergone amputation experience such phantom sensations.⁹ These sensations range from a vague awareness of the presence of the organ via associated paraesthesia to complete sensation including size, shape, position, temperature and movement.¹⁰ Phantom sensations usually diminish in intensity or size over time, but may persist for a long time. ‘Telescoping’ of the phantom part can occur with time such that the phantom limb gradually shrinks proximally to approach the stump.¹¹ Eventually the phantom limb is felt to be within the stump itself.

Phantom Limb Pain

Phantom limb pain (PLP) is defined as any noxious sensory phenomenon of the missing limb or organ. The incidence of phantom limb pain is estimated to be 60–80% after limb amputation.⁵^,⁶ The pain is independent of gender, level or side of amputation.⁵ There is, however, a lower incidence among children and congenital amputees.¹²

Pain can be immediate or delayed in onset. It is typically intermittent and changes with time. Typical characteristics of phantom limb pain are burning, shooting, crushing, throbbing, cramping, aching, tingling, boring; often the limb is described as being in a hyperextended or otherwise unnatural position. The pain usually occurs in the distal portion of the missing limb.⁵ The incidence of pain may be increased if pre-amputation pain was present and may then resemble the pre-amputation pain in character and localisation.⁸^,¹³ However, the exact relationship between pre-amputation pain and PLP is not a simple one, especially as patients’ pain perceptions alter and may be exaggerated with time.⁵ The incidence of phantom pain diminishes with time after amputation, as does the frequency and intensity, being highest immediately following surgery.⁵

It is important to realise, that the terms for noxious syndromes, ‘stump pain’ and ‘phantom limb pain’, are subjective descriptive terms that do not make assumptions on differences in pathophysiology. There is, in fact, a strong correlation between phantom pain and stump pain and they may be interrelated phenomena.¹⁴ All three phenomena can co-exist.⁷

Pathophysiology of Post- Amputation Pain Syndromes

The pathophysiology of post amputation pain syndromes is most likely based on a combination of peripheral and central factors, which interplay subsequent to the significant trauma of an amputation.

Peripheral Factors

The following changes occur after peripheral nerve injury such as cutting of a nerve:¹⁵

1): Sensitization of peripheral nociceptors with a decreased threshold to noxious stimulation;
2): Increased response to supra-threshold stimulation;
3): Spontaneous activity of peripheral receptors due to sensitisation including ectopic pacemaker sites, possibly as a result of the increase in sodium channels, α-adrenergic channels, calcium channels and stretch-activated channels that follows nerve injury;
4): Sensitization of non-nociceptive receptors to nociceptive impulses.

These changes contribute to hyperalgesia and allodynia in the stump; therefore stump manipulation and revision can worsen pain due to repeated deafferentation injuries. The dorsal root ganglion may also be the site of ectopic neuronal activity subsequent to deafferentiation and thereby contributing to pain syndromes.

Furthermore, regrowth of severed nerves often produces nodules called ‘neuromas’. Neuronal activity originating from peripheral neuromas either spontaneously or in response to mechanical, chemical or electrical stimulation, may cause increased sensitivity of the stump to different stimuli.¹⁵

Other peripheral factors include increased muscle tension in the stump correlated with cramping and spasmodic pain and decreased blood flow to stump correlates with descriptions of phantom pain such as burning or tingling. Low stump temperature correlates with burning pain.

Overall, while physical stimulation of the stump may accentuate phantom limb pain, current evidence suggests that peripheral mechanisms do not cause, but at most modulate or perpetuate phantom limb pain.

Spinal Factors

The combination of increased afferent input from sensitised nerve endings and the dorsal root ganglion may contribute to central sensitisation. The following changes occur in the dorsal horn of the spinal cord after nerve injury:¹⁵

1): Increased spontaneous activity of dorsal horn neurones
2): Increased response to afferent input
3): After discharges following repetitive stimulation
4): Expansion of peripheral receptive fields
5): Wind-up (increased neuronal activity in dorsal horn neurons following repetitive C-fibre stimulation), mainly mediated by N-methyl D-aspartate (NMDA) receptors.

These factors play an important role in many chronic pain syndromes, but to which extent these factors are involved in perpetuation of phantom syndromes is currently unclear, although involvement is likely.

Supraspinal Factors

The presence of pain prior to amputation is thought to increase the likelihood of phantom pain.¹³ In 1971, Melzack proposed that the painful extremity had created a painful central ‘engram’. An engram is the schematic representation of body parts in the CNS caused by consistent sensory input. This engram was thought to persist after amputation causing phantom pain.

On the basis of these observations, the neuromatrix theory was proposed by Melzack in 1990.¹⁶ In this theory, the body’s physical self is represented by a matrix, a complex network of neurones connecting somatosensory cortex, thalamus and limbic system. This neuromatrix is genetically determined and subsequently modulated by sensory input, thereby creating a neurosignature for each body part. This neurosignature determines how a body part is consciously perceived; phantom sensations are the result of persistence of the neurosignature after the loss of the limb. The genetic determination of the neurosignature is supported by the observation that children who are born with a missing limb may feel phantom sensations of the missing part.

In this theory, phantom limb pain is the result of abnormal reorganisation in the matrix, either due to a preexisting pain state or the amputation process itself.¹⁶

By analysing neuromagnetic fields, the group around Flor has been able to show a close correlation between the degree of neuromatrix reorganisation and the development of phantom limb pain;¹⁷ reorganisation of somatosensory cortex occurs with neighbouring representation zones moving into the deafferented zone.¹⁸ Here it is also of note that many of the sites of amputation that commonly lead to phantom sensation and pain are sites with a relatively large cortical somatosensory representation.

An alternative theory discussed in the literature is the dynamic reverberation theory. This originated from the observation that selective stereotactic cortectomies of the corona radiata or focal brain lesions in the parietal cortex, thalamus or cortico thalamic fibres on the contralateral side have resulted in permanent relief of phantom pain. This led Canavero, in 1994, to the theory that phantom pain and sensation were a result of a localized dynamic reverberation loop between cortex and thalamus. He postulated that this loop could operate with or without sensory activation.¹⁹

Current Pathophysiological Model of Post-Amputation Pain Syndromes

A comprehensive model incorporating the current state of knowledge has been proposed by Flor et al. It includes peripheral and central factors as relevant contributors to the development and perpetuation of phantom limb pain.¹⁸ In principle, it suggests that somatosensory pain memories and a subsequently altered homuncular representation in the somatosensory cortex are the underlying factors of phantom limb pain, which can be sustained by peripheral factors. In more detail, it assumes that memories of pain established before an amputation are powerful causative contributors to phantom limb pain generation. In analogy to findings in other chronic pain patients, such pain memories increase the representation zone in the primary somatosensory cortex. The changes are then perpetuated after the amputation by selective C-fibre deafferentiation, random input from stump neuromas, abnormal changes in the dorsal root ganglia and the dorsal horn of the spinal cord and sympathetic activation.²⁰

Prevention of Post- Amputation Pain

In view of the immense difficulties in treating phantom limb pain once it is established, considerable efforts have been made to identify techniques to prevent the syndrome. Regrettably, the evidence on none of the methods tried has been conclusive, although overall results of epidural anaesthesia and possibly ketamine administration are promising.

Perioperative Lumbar Epidural Blockade

In 1988, Bach et al. demonstrated that lumbar epidural blockade (LEB) with bupivacaine plus morphine, started 72 hours prior to surgery, reduced the incidence of phantom limb pain in the first year after surgery.²¹ This promising result initiated a number of similar studies; Schug et al. Investigated the use of pre-emptive lumbar epidural anaesthesia/analgesia preoperatively for 24 hours and postoperatively for 72 hours in a small sample of patients. At an interview one year after amputation, those patients with epidural analgesia had significantly less severe phantom limb pain than those receiving general anaesthesia.²²

Another study comparing pre-operative and intra-operative analgesia using LEB showed no difference between groups. The duration of pre operative LEB, however was variable between patients with a median pre operative infusion of 18 hours.²³ However, this study has been criticised for its quality of analgesia and the inclusion of pain of any intensity in the results.

More recently, Lambert and colleagues compared pre-operative epidural with perineural analgesia. The LEB was started 24 hours before surgery and continued for three days post operatively. No difference was found in stump or phantom pain or in phantom sensation at six and 12 months.²⁴ Although this was a randomised trial, the numbers were small and it is questionable whether the study had sufficient power for phantom pain outcome measurements.

In conclusion, there have been several studies looking at preventive analgesia using LEB. The results are conflicting,²⁵ however a meta-analysis showed that perioperative epidural analgesia reduced the incidence of severe phantom limb pain with an NNT of 5.8.²⁶ Overall the results are promising and a protective effect has again been confirmed in a recent audit at our institution.

Peripheral Nerve Blockade

Infusions of local anaesthetics via peripheral nerve sheath catheters, usually inserted by the surgeon during the amputation, are a safe method providing excellent analgesia for the immediate post operative wound pain. They are, however, of no proven benefit in the prevention of phantom pain or stump pain.²⁵

NMDA Antagonists

The use of pre-incision ketamine as pre emptive analgesia has been described previously in other settings. A small observational study suggests that the incidence of severe phantom limb pain may be reduced with the use of ketamine as a bolus followed by an infusion started prior to skin incision and continued for 72 hours postoperatively.²⁷ This promising study was small and used historical controls. A randomised controlled trial could not confirm these results, but was underpowered.²⁸ Epidural ketamine had no preventive effect in an RCT.²⁹ However, a trial of memantine in combination with regional analgesia showed a preventive effect.³⁰ Overall, further investigations are justified.

Evaluation of the Patient With Post-Amputation Pain Syndromes

Phantom sensation requires pre- and postoperative counselling and education but it should not generally pose a clinical problem.

Examination

Examine stump to exclude common causes:

1)

Prosthogenic Pain

a)

Due to an improperly fitting prosthesis:

i): Poor socket fit, cushioning or alignment

b)

Inappropriate suspension resulting in pistoning

c)

Painful adductor roll in the above-knee amputee

d)

Distal residual limb weight-bearing

e)

Poor trim line

2)

Neuropathic Pain

a): Caused by neuroma formation
b): Test for presence of wind-up by examining for Tinel’s sign – shooting pains elicited by repeated tapping over the area

3)

Arthrogenic Pain

a): Pain originating in neighbouring joint or surrounding soft tissue, ligaments or tendons.

4)

Referred Pain

Excessive biomechanical stress in amputees may cause painful musculoskeletal conditions such as sacroiliac dysfunction, piriformis syndrome, facet syndrome or radiculopathy.³¹ Therefore it is important to examine posture and gait.

Furthermore, it is of value to examine skin for areas of ulceration and infection, palpate for areas of tenderness, bony exostosis, heterotropic ossification and adherent scar tissue and evaluate muscle strength and range of movement of neighbouring joints to exclude contracture formation.

Therapy of Post-Amputation Pain Syndromes

A survey by Sherman et al. in 1980 identified over 50 different therapies currently in use for the treatment of phantom limb pain.³² This suggests clearly that an effective treatment of phantom limb pain has not been established and that ‘the results are poor and usually below the expected rate of cure of pain with placebo treatment alone.’

Randomised controlled trials have only established the effectiveness of a small number of therapies.

However, as early treatment is more effective and often multidisciplinary approaches are needed, patients with severe postamputation pain should be promptly referred to a multidisciplinary pain clinic to ensure optimal and timely pain management.

Calcitonin

The parenteral administration of calcitonin is a proven treatment for phantom limb pain and in our experience the most effective in early stages,³³ while there is no benefit in chronic phantom limb pain.³⁴ After initial anecdotal reports,³⁵ a randomised doubleblind cross-over study by Jaeger and Maier showed excellent effectiveness.³⁶ 200 IU of salmon calcitonin was given as an intravenous infusion over 20 minutes and provided complete pain relief for 76% of patients; 71% did not experience recurrence of their phantom pain. Calcitonin may also be given subcutaneously or intra-nasally.³³

The mechanism of action of calcitonin in inhibition or modulation of pain perception is unknown; however anecdotal descriptions of its effectiveness in a number of states of central sensitisation are published. Side effects including dysaesthesia, nausea and vomiting have been described, but most are transient and can be prevented by prophylactic use of antiemetics.³⁶ The risk of an anaphylactic reaction is most likely minimal, but needs to be considered.

Ketamine

Ketamine, an antagonist of the NMDA receptor, is another proven treatment of stump and phantom limb pain. In a randomised trial of patients with existing pain, ketamine has been shown to significantly reduce phantom pain and stump pain. It was also shown to decrease windup like pain (pain evoked by repetitive mechanical stimuli), and to increase the pain-pressure threshold in patients with phantom pain and stump pain. It was given as a bolus of 0.1mg/kg/5minutes followed by an infusion of 7mcg/kg/minute. Pain recurred 30minutes after discontinuation of the infusion in most patients.¹⁵ This was confirmed in a more recent trial.³⁴

Over-activity of NMDA receptors may be a factor in the maintenance of stump pain and phantom pain.

Analgesic and Co-analgesics Compounds

As outlined in the chapter ‘Treatment of Neuropathic Pain’, these agents can play an important role in pain due to nerve injury, but have only variable effects in phantom limb pain.

Opioids

Generally, neuropathic pain is less responsive to opioids than nociceptive pain.³⁷ However, a randomised double-blind study of oral retarded morphine sulphate (MST) showed a significant reduction in phantom pain in opioidsensitive patients, with pain reduction of over 50% occurring in 42% of patients. Neuromagnetic source imaging of three patients suggested reduced cortical reorganization may be occurring with the use of MST.³⁸

A study comparing the effects of intravenous lidocaine with intravenous morphine showed that morphine given as 0.05mg/kg bolus followed by 0.2mg/kg infusion over 40 minutes, given on three consecutive days, significantly reduced both stump and phantom pain.³⁹ An NNT of 5.6 and superiority over mexilitine was found for morphine in a more recent trial.⁴⁰ Tramadol was as effective as amitriptyline in treating post-amputation pain.⁴¹

Gabapentin

In a randomized, double-blind, placebo-controlled, cross over study, six weeks of gabapentin was better than placebo in relieving phantom limb pain. Pain intensity difference was significantly greater for gabapentin than for placebo.⁴² These findings were not confirmed by a later study.⁴³

Clonazepam

Anecdotal evidence suggests that clonazepam may be useful in the treatment of phantom pain.⁴⁴ There are however no studies to confirm this.

Lidocaine

A randomised double blind study comparing the effects of intravenous lidocaine with intravenous morphine showed that lidocaine given as 1mg/kg bolus followed by 4mg/kg infusion, given on three consecutive days, significantly reduced stump pain but had no effect on phantom pain.³⁹

Carbamazepine

There is only anecdotal evidence for the use of carbamazepine in the treatment of post-amputation syndromes.⁴⁵ It has been extensively used in the treatment of other neuropathic pain states. Side effects can be problematic. Randomised trials are required.

Tricyclic Antidepressants (TCA)

In a randomised trial, chlorimipramine, a serotonin reuptake inhibitor, was found to be significantly better than nortriptyline, a noradrenaline reuptake inhibitor, in the treatment of central pain syndromes.⁴⁶ Amitriptyline and tramadol were equally effective in the treatment of phantom limb pain.⁴¹

Selective Serotonin Reuptake Inhibitors

Venlafaxine is a serotonin and noradrenaline reuptake inhibitor with a side-effect profile significantly better than TCAs.⁴⁷ There are no RCTs on its effect on post-amputation pain syndromes.

Baclofen

This gamma-aminobutyric acid (GABA) agonist, when given intrathecally, has been shown to reduce chronic musculoskeletal pain.⁴⁸ It may therefore be of some benefit if muscle spasm is the source of the pain. It has not been proven to be of use in phantom limb pain.

Capsaicin

Capsaicin depletes the neurotransmitter, substance P from sensory nerves and may give relief to some patients with stump pain when used topically.⁴⁹

Symptomatic Treatment of Pain Components

The burning component of phantom limb pain alone can be decreased by pharmacological and behavioural therapies that increase the temperature of the stump such as sympathectomy, α-or β-blockade or biofeedback.

Cramping can be relieved by treatments that reduce muscle tension, for example with the use of baclofen or again biofeedback.

Nonpharmacological Therapies

The following therapies are thought to relieve phantom pain by causing increased sensory inflow into the stump area:

TENS
Acupuncture
Physical therapy

With the development of theories on cortical reorganisation as a cause for phantom limb pain, there are now therapies tried, which are based on the concept of reversing such reorganisation.¹⁸ Sensory discrimination training programs show promise here; this is a process during which patients have to discriminate the frequency or location of high intensity, non-painful electrical stimuli applied through electrodes on their stump in an attempt to separate merged regions on their cortical somatosensory map.

A recent study using this technique showed that phantom limb pain was significantly decreased in the group who underwent the training process compared to controls. Cortical reorganisation, assessed by neuroelectric source imaging and structural magnetic resonance imaging, was also reduced in this group.⁵⁰ Mental imagery of limb movement⁵¹^,⁵² and a combination of laterality recognition, mirror movements and imagined movements are other successful approaches based on this concept.⁵³

Similarly, there are now first data, that use of a myoelectric prosthesis may prevent cortical reorganisation and phantom limb pain.⁵⁴

Invasive Therapies

Electroconvulsive Therapy (ECT)

This psychiatric treatment is thought to interrupt the dynamic reverberations that maintain central and phantom pain in the thalamocortical pathway¹⁹ and has been used in the treatment of refractory phantom pain.⁵⁵ There have been no trials in this area.

Nerve Blockade

There is only anecdotal evidence for the use of peripheral nerve blockade in the treatment of phantom pain syndromes.⁵⁶ There have been no trials in this area.

Spinal Cord Stimulation

Tis treatment, thought to facilitate inhibitory descending pathways, has been described in the treatment of phantom pain. The overall success rate of this expensive and invasive approach in this indication is in the range of less than 50%.⁵⁷^,⁵⁸

Implantable Intrathecal Delivery Systems

Infusing clonidine, local anesthetic, baclofen or opioids, usually in a combination, may be beneficial in selected patients with phantom limb pain, although there are no definitive studies.

Dorsal Root Entry Zone (DREZ) Lesions

DREZ lesioning has a limited effect for a limited time only in phantom limb pain;⁵⁹ this is in line with clinical experience with this neurodestructive approach. Other types of surgery and neuroablation often makes pain worse because of repeated stimulation and/or deafferentation of the affected nerves.

Psychological Therapy

Pre-amputation counselling is mandatory as amputees go through normal grieving processes. It is important to identify anxiety and depression early as these can magnify pain perception. Behavioural, cognitive, group therapy and pain management programs are all useful methods of helping patients cope with their pain. Hypnosis, biofeedback and muscular relaxation training to disrupt the pain-anxiety-tension cycle are important components of chronic pain therapy.⁶⁰

Future Aims

Future aims in the management of post amputation syndromes focus on:

1): Further prospective randomised trials to evaluate the benefits of current pharmacological therapies.
2): Clarification of the role of pre-emptive analgesia in the prevention of phantom pain.
3): Evaluation of the promising methods that attempt to revert the cortical reorganization that occurs following amputation towards normal.
4): A multi-modal and multi-disciplinary approach to pain management.

References

1.: Furukawa T. Charles Bell’s description of the phantom phenomenon in 1830. Neurology 1990; 40: 1830. [PubMed: 2247229]
2.: Dijkstra PU, Rietman JS, Geertzen JH. Phantom breast sensations and phantom breast pain: a 2–year prospective study and a methodological analysis of literature. Eur J Pain 2007; 11: 99–108. [PubMed: 16487732]
3.: Marbach JJ, Raphael KG. Phantom tooth pain: a new look at an old dilemma. Pain Med 2000; 1: 68–77. [PubMed: 15101965]
4.: Boas RA, Schug SA, Acland RH. Perineal pain after rectal amputation: a 5–year follow-up. Pain 1993; 52: 67–70. [PubMed: 8446438]
5.: Nikolajsen L, Jensen TS. Phantom limb pain. Br J Anaesth 2001; 87: 107–16. [PubMed: 11460799]
6.: Kern U, Busch V, Rockland M, et al. [Prevalence and risk factors of phantom limb pain and phantom limb sensations in Germany: A nationwide field survey.]. Schmerz 2009. [PubMed: 19322592]
7.: Nikolajsen L, Ilkjaer S, Kroner K, et al. The influence of preamputation pain on postamputation stump and phantom pain. Pain 1997; 72: 393–405. [PubMed: 9313280]
8.: Hanley MA, Jensen MP, Smith DG, et al. Preamputation pain and acute pain predict chronic pain after lower extremity amputation. J Pain 2007; 8: 102–9. [PubMed: 16949876]
9.: Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain 1983; 17: 243–56. [PubMed: 6657285]
10.: Giummarra MJ, Gibson SJ, Georgiou-Karistianis N, Bradshaw JL. Central mechanisms in phantom limb perception: the past, present and future. Brain Res Rev 2007; 54: 219–32. [PubMed: 17500095]
11.: Giummarra MJ, Georgiou-Karistianis N, Nicholls ME, et al. Corporeal awareness and proprioceptive sense of the phantom. Br J Psychol 2010; 101: 791–808. [PubMed: 20346204]
12.: Wilkins KL, McGrath PJ, Finley GA, Katz J. Phantom limb sensations and phantom limb pain in child and adolescent amputees. Pain 1998; 78: 7–12. [PubMed: 9822207]
13.: Katz J, Melzack R. Pain ‘memories’ in phantom limbs: review and clinical observations. Pain 1990; 43: 319–336. [PubMed: 2293143]
14.: Kooijman CM, Dijkstra PU, Geertzen JH, et al. Phantom pain and phantom sensations in upper limb amputees: an epidemiological study. Pain 2000; 87: 33–41. [PubMed: 10863043]
15.: Nikolajsen L, Hansen CL, Nielsen J, et al. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input. Pain 1996; 67: 69–77. [PubMed: 8895233]
16.: Melzack R. From the gate to the neuromatrix. Pain 1999; Suppl 6: S121–6. [PubMed: 10491980]
17.: Flor H, Elbert T, Knecht S, et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 1995; 375: 482–4. [PubMed: 7777055]
18.: Flor H. Maladaptive plasticity, memory for pain and phantom limb pain: review and suggestions for new therapies. Expert Rev Neurother 2008; 8: 809–18. [PubMed: 18457537]
19.: Canavero S. Dynamic reverberation. A unified mechanism for central and phantom pain. Med Hypotheses 1994; 42: 203–7. [PubMed: 8057978]
20.: Flor H, Birbaumer N, Sherman RA. Phantom Limb Pain. Pain Clinical Updates 2000; 8: 1–7.
21.: Bach S, Nreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988; 33: 297–301. [PubMed: 3419837]
22.: Schug SA, Burrell R, Pane J, Teter P. Pre-emptive epidural analgesia may prevent phantom limb pain. Regional Anesthesia 1995; 20: 256. [PubMed: 7547671]
23.: Nkolajsen L, Ilkjaer S, Jensen T. Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth 1998; 81: 348–54. [PubMed: 9861117]
24.: Lambert AW, Dashfield AK, Cosgrove C, et al. Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation. Reg Anesth Pain Med 2001; 26: 316–21. [PubMed: 11464349]
25.: Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic phantom pain: a systematic review. Clin J Pain 2002; 18: 84–92. [PubMed: 11882771]
26.: Gehling M, Tryba M. [Prophylaxis of phantom pain: is regional analgesia ineffective?]. Schmerz 2003; 17: 11–9. [PubMed: 12579385]
27.: Dertwinkel R, Heinrichs C, Senne I, et al. Prevention of severe phantom limb pain by perioperative administration of ketamine – An observational study. Acute Pain 2002; 4: 12–16.
28.: Hayes C, Armstrong-Brown A, Burstal R. Perioperative intravenous ketamine infusion for the prevention of persistent post-amputation pain: a randomized, controlled trial. Anaesth Intensive Care 2004; 32: 330–8. [PubMed: 15264726]
29.: Wilson JA, Nimmo AF, Fleetwood-Walker SM, Colvin LA. A randomised double blind trial of the effect of pre emptive epidural ketamine on persistent pain after lower limb amputation. Pain 2008; 135: 108–18. [PubMed: 17583431]
30.: Schley M, Topfner S, Wiech K, et al. Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain 2007; 11: 299–308. [PubMed: 16716615]
31.: Davis RW. Phantom sensation, phantom pain, and stump pain. Arch Phys Med Rehabil 1993; 74: 79–91. [PubMed: 8380543]
32.: Sherman RA, Sherman CJ, Gall NG. A survey of current phantom limb pain treatment in the United States. Pain 1980; 8: 85–99. [PubMed: 6988765]
33.: Wall GC, Heyneman CA. Calcitonin in phantom limb pain. Ann Pharmacother 1999; 33: 499–501. [PubMed: 10332543]
34.: Eichenberger U, Neff F, Sveticic G, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg 2008; 106: 1265–73, table of contents. [PubMed: 18349204]
35.: Jaeger H, Maier C, Wawersik J. [Postoperative treatment of phantom pain and causalgias with calcitonin]. Anaesthesist 1988; 37: 71–6. [PubMed: 3364666]
36.: Jaeger H, Maier C. Calcitonin in phantom limb pain: a double-blind study. Pain 1992; 48: 21–7. [PubMed: 1738570]
37.: Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988; 33: 11–23. [PubMed: 2454440]
38.: Huse E, Larbig W, Flor H, Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization. Pain 2001; 90: 47–55. [PubMed: 11166969]
39.: Wu CL, Telia P, Staats PS, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial. Anesthesiology 2002; 96: 841–8. [PubMed: 11964590]
40.: Wu CL, Agarwal S, Telia PK, et al. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Anesthesiology 2008; 109: 289–96. [PMC free article: PMC2654208] [PubMed: 18648238]
41.: Wilder-Smith CH, Hill LT, Laurent S. Postamputation pain and sensory changes in treatment-naive patients: characteristics and responses to treatment with tramadol, amitriptyline, and placebo. Anesthesiology 2005; 103: 619–28. [PubMed: 16129989]
42.: Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Reg An esth Pain Med 2002; 27: 481–6. [PubMed: 12373695]
43.: Nikolajsen L, Finnerup NB, Kramp S, et al. A randomized study of the effects of gabapentin on postamputation pain. Anesthesiology 2006; 105: 1008–15. [PubMed: 17065896]
44.: Bartusch SL, Sanders BJ, D’Alessio JG, Jernigan JR. Clonazepam for the treatment of lancinating phantom limb pain. Clin J Pain 1996; 12: 59–62. [PubMed: 8722737]
45.: Patterson JF. Carbamazepine in the treatment of phantom limb pain. South Med J 1988; 81: 1100–2. [PubMed: 3047877]
46.: Panerai AE, Monza G, Movilia P, et al. A randomized, within-patient, crossover, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Acta Neurol Scand 1990; 82: 34–8. [PubMed: 2239134]
47.: Mattia C, Paoletti F, Coluzzi F, Boanelli A. New antidepressants in the treatment of neuropathic pain. A review. Minerva Anestesiol 2002; 68: 105–14. [PubMed: 11981519]
48.: Loubser PG, Akman NM. Effects of intrathecal baclofen on chronic spinal cord injury pain. J Pain Symptom Manage 1996; 12: 241–7. [PubMed: 8898508]
49.: Cannon DT, Wu Y. Topical capsaicin as an adjuvant analgesic for the treatment of traumatic amputee neurogenic residual limb pain. Arch Phys Med Rehabil 1998; 79: 591–3. [PubMed: 9596406]
50.: Flor H, Denke C, Schaefer M, Grusser S. Effect of sensory discrimination training on cortical reorganisation and phantom limb pain. Lancet 2001; 357: 1763–4. [PubMed: 11403816]
51.: Maciver K, Lloyd DM, Kelly S, et al. Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain 2008; 131: 2181–91. [PMC free article: PMC2494616] [PubMed: 18567624]
52.: Ulger O, Topuz S, Bayramlar K, et al. Effectiveness of phantom exercises for phantom limb pain: a pilot study. J Rehabil Med 2009; 41: 582–4. [PubMed: 19543671]
53.: Moseley GL. Graded motor imagery for pathologic pain: a randomized controlled trial. Neurology 2006; 67: 2129–34. [PubMed: 17082465]
54.: Lotze M, Grodd W, Birbaumer N, et al. Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? Nat Neurosci 1999; 2: 501–2. [PubMed: 10448212]
55.: Rasmussen KG, Rummans TA. Electroconvulsive therapy for phantom limb pain. Pain 2000; 85: 297–9. [PubMed: 10692632]
56.: Lierz P, Schroegendorfer K, Choi S, et al. Continuous blockade of both brachial plexus with ropivacaine in phantom pain: a case report. Pain 1998; 78: 135–7. [PubMed: 9839824]
57.: Katayama Y, Yamamoto T, Kobayashi K, et al. Motor cortex stimulation for phantom limb pain: comprehensive therapy with spinal cord and thalamic stimulation. Stereotact Funct Neurosurg 2001; 77: 159–62. [PubMed: 12378068]
58.: Kumar K, Toth C, Nath RK, Laing p. Epidural spinal cord stimulation for treatment of chronic pain – some predictors of success. A 15–year experience. Surg Neurol 1998; 50: 110–20. [PubMed: 9701116]
59.: Garcia March G, Sanchez-Ledesma MJ, Diaz P, et al. Dorsal root entry zone lesion versus spinal cord stimulation in the management of pain from brachial plexus avulsion. Acta Neurochir Suppl (Wien) 1987; 39: 155–8. [PubMed: 2823541]
60.: Sherman RA, Gall N, Gormly J. Treatment of phantom limb pain with muscular relaxation training to disrupt the pain – anxiety – tension cycle. Pain 1979; 6: 47–55. [PubMed: 370738]

Bookshelf ID: NBK534280PMID: 30485033

Contents