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Cellular and Molecular Life Sciences

, Volume 74, Issue 18, pp 3275–3291 | Cite as

Chemokines in neuron–glial cell interaction and pathogenesis of neuropathic pain

  • Zhi-Jun Zhang
  • Bao-Chun Jiang
  • Yong-Jing Gao
Review

Abstract

Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron–glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

Keywords

Neuroinflammation Astrocytes Microglia Spinal cord Chronic pain 

Abbreviations

AD

Alzheimer’s disease

AMPA

Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate

BCP

Bone cancer pain

CCI

Chronic constriction injury

CFA

Complete Freund’s adjuvant

CNS

Central nervous system

CSF

Cerebrospinal fluid

DRG

Dorsal root ganglion

EAE

Experimental autoimmune encephalomyelitis

ERK

Extracellular signal-regulated kinase

EPSC

Excitatory postsynaptic currents

GABA

Gamma-aminobutyric acid

IL

Interleukin

IAMNT

Inferior alveolar nerve and mental nerve transection

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

MCP-1

Monocytes chemoattractant protein-1

MS

Multiple sclerosis

LTP

Long-term potentiation

NMDA

N-methyl-d-aspartic acid

pIONL

Partial infraorbital nerve ligation

PNS

Peripheral nervous system

pSNL

Partial sciatic nerve ligation

SNL

Spinal nerve ligation

SNI

Spared nerve injury

TNF-α

Tumor necrosis factor-alpha

TG

Trigeminal ganglion

Notes

Acknowledgements

This study was supported by the grants from the National Natural Science Foundation of China (NSFC 31371121, 81400915, 81571070, and 31671091), the National Science Foundation for Young Scientists of Jiangsu Province (BK20140427), the Qing Lan Project, and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Department of Human Anatomy, School of MedicineNantong UniversityNantongChina
  2. 2.Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of NeuroregenerationNantongChina
  3. 3.Co-innovation Center of NeuroregenerationNantong UniversityNantongChina

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