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


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.


Neuroinflammation Astrocytes Microglia Spinal cord Chronic pain 



Alzheimer’s disease




Bone cancer pain


Chronic constriction injury


Complete Freund’s adjuvant


Central nervous system


Cerebrospinal fluid


Dorsal root ganglion


Experimental autoimmune encephalomyelitis


Extracellular signal-regulated kinase


Excitatory postsynaptic currents


Gamma-aminobutyric acid




Inferior alveolar nerve and mental nerve transection


c-Jun N-terminal kinase


Mitogen-activated protein kinase


Monocytes chemoattractant protein-1


Multiple sclerosis


Long-term potentiation


N-methyl-d-aspartic acid


Partial infraorbital nerve ligation


Peripheral nervous system


Partial sciatic nerve ligation


Spinal nerve ligation


Spared nerve injury


Tumor necrosis factor-alpha


Trigeminal ganglion



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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