title: CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model.
abstract: BACKGROUND
  Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases.
  
  
  METHODS
  Immunofluorescence staining, western blot analysis, and RT-PCR were used to investigate the modulatory effects of CD200 fusion protein (CD200Fc) on activation of microglia and astrocytes as well as synthesis of pro- (TNF, IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in the L4-L5 spinal cord segments in relation to behavioral signs of neuropathic pain after unilateral sterile chronic constriction injury (sCCI) of the sciatic nerve. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were measured in hind paws 1 day before operation; 1, 3, and 7 days after sCCI operation; and then 5 and 24 h after intrathecal application of artificial cerebrospinal fluid or CD200Fc.
  
  
  RESULTS
  Seven days from sCCI operation and 5 h from intrathecal application, CD200Fc reduced mechanical and thermal hypersensitivity when compared with control animals. Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels. Administration of CD200Fc also diminished elevation of CD200 and CD200R proteins as a concomitant reaction of the modulatory system to increased neuroinflammatory reactions after nerve injury. The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application.
  
  
  CONCLUSIONS
  Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development. This may constitute a promising and novel therapeutic approach for the treatment of neuropathic pain.
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. mirihh@hotmail.com.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hernangómez
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. iklusak@med.muni.cz.|Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. iklusak@med.muni.cz.
authors.forename: Ilona
authors.initials: I
authors.lastname: Klusáková
authors.affiliation: Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. joukal@med.muni.cz.
authors.forename: Marek
authors.initials: M
authors.lastname: Joukal
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. isvizen@med.muni.cz.|Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. isvizen@med.muni.cz.
authors.forename: Ivana
authors.initials: I
authors.lastname: Hradilová-Svíženská
authors.affiliation: Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. cgjb@cajal.csic.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. pdubovy@med.muni.cz.|Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. pdubovy@med.muni.cz.
authors.forename: Petr
authors.initials: P
authors.lastname: Dubový
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D064446:Orexin Receptors; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D012585:Sciatica / Q000150:complications* / Q000188:drug therapy; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; C042739:antigens, CD200