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  • Review Article
  • Published:

Structural plasticity and reorganisation in chronic pain

An Erratum to this article was published on 20 January 2017

Key Points

  • The transition from acute to chronic pain is associated with structural plasticity or circuit reorganisation at various points in somatosensory pain circuits.

  • Peripheral sensory neurons and axons exhibit diverse types of structural changes that are specific to different types of chronic pain.

  • Structural remodelling of synaptic contacts on spinal dorsal horn neurons is causally associated with nociceptive hypersensitivity.

  • Neuropathic pain is associated with the reorganization of cortical sensory maps.

  • Chronic pain is characterized by increased pain-related activation of emotional networks in the brain.

  • Pain disrupts structural and functional brain connectivity, which can be restored with effective treatment.

Abstract

Chronic pain is not simply a temporal continuum of acute pain. Studies on functional plasticity in neural circuits of pain have provided mechanistic insights and linked various modulatory factors to a change in perception and behaviour. However, plasticity also occurs in the context of structural remodelling and reorganisation of synapses, cells and circuits, potentially contributing to the long-term nature of chronic pain. This Review discusses maladaptive structural plasticity in neural circuits of pain, spanning multiple anatomical and spatial scales in animal models and human patients, and addresses key questions on structure–function relationships.

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Figure 1: Nociceptive, activity-dependent presynaptic and postsynaptic plasticity at nociceptive synapses in spinal superficial laminae.
Figure 2: Models of changes in spinal circuitry segregating pain from innocuous touch in neuropathic mechanical allodynia.
Figure 3: Structural and functional changes in the human brain in chronic pain conditions.

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Acknowledgements

The authors acknowledge all scientists in the Collaborative Research Center 1158 (SFB1158) in Heidelberg/Mannheim for valuable discussions on this topic. The authors thank R. LeFaucheur for secretarial help and acknowledge funding in form of SFB1158 grants from the Deutsche Forschungsgemeinschaft (DFG) to R.K. and H.F., as well as European Research Council (ERC) Advanced Investigator grants to R.K. (Pain Plasticity 294293) and H.F. (Phantommind 230249). R.K. and H.F. are principal investigators in the Excellence Cluster 'Cellular Networks' of Heidelberg University and acknowledge the support by EcTop3. The authors apologize to those colleagues in the field whose work could not be discussed and cited owing to space restrictions.

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Correspondence to Rohini Kuner or Herta Flor.

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PowerPoint slides

Glossary

Nociception

The sensing of stimuli that are potentially harmful to the body; the sensory component of pain.

Acute pain

A transient form of pain that is acutely associated with a nociceptive stimulus.

Chronic pain

A pain that persists for long periods of time and, in most cases, extends beyond the period of healing of the original insult or injury.

Plasticity

The ability to change in an activity-dependent manner; it encompasses both structural and functional changes.

Chronic back pain

A pain that is associated with the back and that lasts longer than the expected period of healing. It can have neuropathic or inflammatory components, or both, but, in many cases, has no clear aetiology.

Complex regional pain syndrome

(CRPS). A chronic type of pain that typically affects a limb after trauma or injury and that can have inflammatory and neuropathic components.

Post-amputation pain

Acute and chronic pain that is caused by amputations. It can include postoperative pain, pain in the residual limb and pain in the amputated limb, referred to as phantom limb pain.

Allodynia

A pain or unpleasant sensations in response to a normally innocuous stimulus, such as a tactile stimulation (mechanical allodynia) or a mild change in temperature (mostly cold allodynia).

Pain behaviour

Behavioural changes (occurring both in the context of animal models of pain and in humans experiencing pain) that are indicative of pain. They can be of a spontaneous, ongoing nature or evoked by application of a noxious or innocuous stimulus.

Hyperalgesia

An exaggerated sensitivity and perception of pain in response to nociceptive stimuli.

Painful neuropathy

A chronic pain that is causally associated with lesions of peripheral or central neurons.

Knee osteoarthritis

A pain that is caused by wearing away of the cartilage in knee joints.

Bone metastatic pain

A class of cancer-associated pain that is caused by metastatic tumour growth in skeletal bones.

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Kuner, R., Flor, H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci 18, 20–30 (2017). https://doi.org/10.1038/nrn.2016.162

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