title: Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.
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.
authors.affiliation: Department of Human Anatomy, School of Medicine, Nantong University, Nantong, Jiangsu, 226001, China.|Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong, Jiangsu, 226001, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong, Jiangsu, 226001, China.
authors.forename: Bao-Chun
authors.initials: BC
authors.lastname: Jiang
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong, Jiangsu, 226001, China. gaoyongjing@hotmail.com.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, China. gaoyongjing@hotmail.com.
authors.forename: Yong-Jing
authors.identifier: 0000-0002-7432-7458
authors.initials: YJ
authors.lastname: Gao
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine
keywords: Astrocytes; Chronic pain; Microglia; Neuroinflammation; Spinal cord