CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway

• Published in: Journal of neuroscience research Vol. 91; no. 4; pp. 545 - 553
• Main Authors: Sun, Jian-Liang, Xiao, Chun, Lu, Bo, Zhang, Juan, Yuan, Xiao-zong, Chen, Wei, Yu, Li-Na, Zhang, Feng-Jiang, Chen, Gang, Yan, Min
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2013; Wiley Subscription Services, Inc
• Subjects: Animals; Antisense oligonucleotides; Chemokine CX3CL1 - genetics; Chemokine CX3CL1 - metabolism; CX3CL1; extracellular signal-regulated protein kinase 5; Hyperalgesia - etiology; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Male; microglia; Mitogen-Activated Protein Kinase 7 - genetics; Mitogen-Activated Protein Kinase 7 - metabolism; Neuralgia - complications; Neuralgia - metabolism; Neuralgia - physiopathology; neuropathic pain; Oligodeoxyribonucleotides, Antisense; Phosphorylation; Rats; Rats, Sprague-Dawley; Signal Transduction - physiology; Spinal Cord Injuries - complications; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Spinal Nerves - injuries; Spinal Nerves - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23168

Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal‐regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. The knockdown of ERK5 by intrathecal injection of antisense oligonucleotides suppressed the hyperalgesia and nuclear impact of nuclear factor‐κB induced by SNL. The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1‐induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury‐induced pain hypersensitivity through the ERK5 signaling pathway. © 2013 Wiley Periodicals, Inc.