title: [Role of the CX3CR1/ERK5 pathway in spinal microglia for the development of neuropathic pain].
abstract: OBJECTIVE
  To explore the role of spinal microglial CX3CR1/ERK5 pathway in the development of neuropathic pain.
  
  
  METHODS
  The model of spinal nerve ligation (SNL) was established by ligating the L5 spinal nerve with 6-0 silk thread in male Sprague Dawley rats. The expression of activated ERK5 (p-ERK5) was examined by immunohistochemistry test. To detect the role of ERK5 in neuropathic pain, PWT and PWL were measured after an intrathecal knockdown of ERK5. For determining the regulating effect of CX3CL1/CX3CR1 on the activity of microglial ERK5, CX3CR1 was blocked by an intrathecal injection of anti-rat CX3CR1 antibody and the activity of spinal ERK5 tested. Then whether an intrathecal knockdown of ERK5 could reverse the effect of CX3CL1 on pain hypersensitivity and microglia activation was investigated.
  
  
  RESULTS
  ERK5 was activated in spinal microglia after SNL compared to the sham group (61.75 ± 11.52 vs 2.2 ± 0.12; 58.01 ± 10.45 vs 1.1 ± 0.11) . The knockdown of ERK5 by an intrathecal injection of antisense oligonucleotides suppressed the mechanical (15.42 ± 3.46 vs 22.73 ± 3.21g; 13.63 ± 2.88 vs. 21.42 ± 4.12g) and thermal hyperalgesia (13.48 ± 2.01) vs (18.05 ± 3.71) s; (11.6 ± 2.33) vs (17.73 ± 1.42) s induced by nerve injury. The blockage of CX3CR1, a receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL (30.12 ± 8.60) vs (58.25 ± 11.5); (49.5 ± 12.12) vs (35.51 ± 3.74) (P < 0.05). In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation.
  
  
  CONCLUSIONS
  CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through ERK5.
authors.affiliation: Department of Anesthesiology, Wenzhou Medical College, Wenzhou 324027, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Juan
authors.initials: J
authors.lastname: Yao
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Lei
authors.forename: Chun
authors.initials: C
authors.lastname: Xiao
authors.forename: Jian-liang
authors.initials: JL
authors.lastname: Sun
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction; D013127:Spinal Nerves
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D019707:Receptors, Chemokine; D048054:Mitogen-Activated Protein Kinase 7