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  • Review Article
  • Published:

Phantom limb pain: a case of maladaptive CNS plasticity?

Nature Reviews Neuroscience volume 7, pages 873–881 (2006)Cite this article

Key Points

  • Despite many advances in medicine, phantom limb pain — pain in a no longer existing or deafferented limb — still occurs in 50–80% of all amputees.

  • Pathological neuronal activity in the residual limb or the dorsal root ganglion, which can be enhanced by sympathetic activation, could be one important factor in phantom limb pain.

  • Spinal changes include reorganization of the body map as well as sensitization of spinal transmission neurons.

  • Supraspinal changes seem to be important and might have a special focus in the cortex, where maladaptive map reorganization has been found to be closely related to the magnitude of phantom pain.

  • Similarities of phantom limbs and phantom pain to other abnormal sensory phenomena such as somatosensory and body image-related illusions suggest that frontal and parietal brain regions might be important in the generation of phantom limbs and phantom pain.

  • Previous painful experience could culminate in a pain memory that might have a role in phantom pain and involve both sensory and affective components.

  • Behavioural interventions such as use of a mirror, imagery, sensory discrimination training or use of a myoelectric prosthesis could reduce maladaptive plastic changes and subsequently phantom limb pain; pharmacological interventions and stimulation methods might be similarly effective.

Abstract

Phantom pain refers to pain in a body part that has been amputated or deafferented. It has often been viewed as a type of mental disorder or has been assumed to stem from pathological alterations in the region of the amputation stump. In the past decade, evidence has accumulated that phantom pain might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human studies and derive suggestions for innovative interventions aimed at alleviating phantom pain.

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Figure 1: A schematic diagram of the areas involved in the generation of phantom limb pain and the main peripheral and central mechanisms.
Figure 2: Cortical changes related to phantom limb pain.
Figure 3: Brain correlates of the telescoping phenomenon.

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Acknowledgements

This article is dedicated to the memory of T. Pons, whose work inspired many of the findings reported here. This work was supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung (German Neuropathic Pain Network) and the Lundbeck Foundation, Denmark. The authors would like to thank W. Jänig for helpful comments on an earlier version of this article and M. Lotze for help with the figures.

Author information

Authors and Affiliations

  1. Department of Clinical and Cognitive Neuroscience, University of Heidelberg, Central Institute of Mental Health, Mannheim, D-68159, Germany

    Herta Flor

  2. Department of Anesthesiology and Danish Pain Research Center, Aarhus University Hospital, Aarhus C, DK-8000, Denmark

    Lone Nikolajsen

  3. Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus C, DK-8000, Denmark

    Troels Staehelin Jensen

Authors
  1. Herta Flor
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  2. Lone Nikolajsen
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  3. Troels Staehelin Jensen
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Corresponding author

Correspondence to Herta Flor.

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FURTHER INFORMATION

Flor's laboratory

Glossary

Neuroma

When a limb is severed, a terminal swelling or 'endbulb' is formed and axonal sprouting occurs. In the case of an amputation, sprouting and endbulb formation lead to a neuroma, a tangled mass that forms when the axons cannot reconnect or can only partially reconnect, as is the case in partial lesions. These neuromas generate abnormal activity that is called ectopic because it does not originate from the nerve endings.

Dorsal root ganglion

A nodule on a dorsal root that contains cell bodies of afferent spinal neurons, which convey somatosensory input to the CNS.

Paraesthesia

An abnormal skin sensation such as tingling or itching.

Microglia

Glial cells are the 'glue' of the nervous system, and support and protect the neurons. Microglia are a special form of small glial cells; they have immune functions and can be involved in inflammatory actions.

Substance P

A neuropeptide that plays an important role in nociception and is released by the primary somatosensory afferents in the spinal cord.

C-afferents

Unmyelinated fibres, 0.4–1.2 μm in diameter, conducting nerve impulses at a velocity of 0.7–2.3 ms−1. They conduct secondary, delayed pain.

Aδ afferents

Thinly myelinated nerve fibres with a conduction velocity of 10–30 ms−1 that convey nociceptive information to the spinal cord. These receptors convey first, sharp, pricking pain and are located mainly on hairy skin.

Aβ fibres

Large-diameter myelinated fibres that have a conduction velocity of ∼40 ms−1 and normally carry non-nociceptive information.

Myoelectric prosthesis

A motor-driven prosthesis that can, for example, be used for grip movements and is operated through the use of electromyographic signals from muscles.

Complex regional pain syndrome

(CRPS). A chronic neuropathic pain syndrome of two types. CRPS1 occurs most often in the arms or legs after a minor or major injury and is accompanied by severe pain, swelling, oedema, sudomotor abnormalities and increased sensitivity to touch. CRPS2 is related to an identified nerve injury.

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Flor, H., Nikolajsen, L. & Staehelin Jensen, T. Phantom limb pain: a case of maladaptive CNS plasticity?. Nat Rev Neurosci 7, 873–881 (2006). https://doi.org/10.1038/nrn1991

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