Korean J Physiol Pharmacol.  2016 Jan;20(1):1-8. 10.4196/kjpp.2016.20.1.1.

Neural circuit remodeling and structural plasticity in the cortex during chronic pain

Affiliations
  • 1Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. skkim77@khu.ac.kr

Abstract

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

Keyword

Chronic pain; Neural circuit remodeling; Pain matrix; Structural synaptic plasticity; Two-photon microscopy

MeSH Terms

Animals
Brain
Chronic Pain*
Fluorescence
Gyrus Cinguli
Humans
Microscopy
Models, Animal
Nervous System
Neuroimaging
Neurons
Plastics*
Prefrontal Cortex
Somatosensory Cortex
Spinal Cord
Synapses
Plastics

Figure

  • Fig. 1 In vivo two-photon microscopy imaging in the cortex of living animals.(a) Comparison of conventional single photon microscopy and two-photon microscopy imaging in the intact cortex of YFP-H line mouse [61], expressing yellow fluorescent proteins (YFPs) in many layer V pyramidal neurons. [Left] Representative 3D reconstructed single photon (confocal) microscopy image of layer V pyramidal neurons in the S1 cortex of anesthetized YFP-H mouse. Note that only distal dendrites, not proximal dendrites and cell bodies, of layer V pyramidal neurons can be seen up to 200~300 µm deep from the surface, for which full laser power should be used. Scale bar, 100 µm. [Middle-top] Characteristics of single photon imaging (left) and two-photon imaging (right). [Middle-bottom] Schematic drawing of in vivo two-photon imaging of neurons in a living mouse. [Right] Representative 3D reconstructed two-photon microscopy image of layer V pyramidal neurons in the S1 cortex of anesthetized YFP-H mouse. Note that whole parts of dendrites and cell bodies of layer 5 pyramidal neurons are clearly seen up to 600 µm deep from the surface. Scale bar, 100 µm. (b) Little change in dendritic arbors in nerve injured mice over 3 weeks. [Left] Z-projection image of apical dendrites (512×512 pixels, 0.62 µm/pixels, 50 optical planes, 1 µm step, 10~60 µm below the surface) in the S1 cortex taken just before peripheral nerve injury. [Right] Image of the same dendrites taken after peripheral nerve injury. Scale bar, 50 µm. (c) Representative images of the same dendrite in the S1 cortex taken before and after peripheral nerve injury. Arrowheads indicate dendritic spines generated (red) or eliminated (blue) when compared with the previous imaging session. Note the increase of spine formation and elimination after peripheral nerve injury. Scale bar, 2 µm.


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