title: Elevated expression of fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in the dorsal root ganglia and spinal cord in experimental autoimmune encephalomyelitis: implications in multiple sclerosis-induced neuropathic pain.
abstract: Multiple sclerosis (MS) is a central nervous system (CNS) disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP). Molecular signaling through fractalkine (CX3CL1), a nociceptive chemokine, via its receptor (CX3CR1) is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE) model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG) and spinal cord (SC) 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG/SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Apotex Center 750, McDermot Avenue, Winnipeg, MB, Canada R3E 0T5.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhu
authors.forename: Crystal
authors.initials: C
authors.lastname: Acosta
authors.forename: Brian
authors.initials: B
authors.lastname: MacNeil
authors.forename: Claudia
authors.initials: C
authors.lastname: Cortes
authors.forename: Howard
authors.initials: H
authors.lastname: Intrater
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
authors.forename: Mike
authors.initials: M
authors.lastname: Namaka
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000473:pathology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D017628:Microglia; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D012333:RNA, Messenger; D019707:Receptors, Chemokine