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CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model.
- Source :
-
Journal of neuroinflammation [J Neuroinflammation] 2016 Feb 18; Vol. 13, pp. 43. Date of Electronic Publication: 2016 Feb 18. - Publication Year :
- 2016
-
Abstract
- Background: Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Antigens, CD metabolism
Antigens, Surface pharmacology
Cytokines genetics
Disease Models, Animal
Gene Expression Regulation drug effects
Glial Fibrillary Acidic Protein metabolism
Hyperalgesia drug therapy
Inflammation drug therapy
Inflammation metabolism
Injections, Spinal
Male
Neuroglia drug effects
Neuroglia metabolism
Orexin Receptors
Pain Threshold drug effects
Physical Stimulation adverse effects
Rats
Rats, Wistar
Receptors, Cell Surface antagonists & inhibitors
Sciatica drug therapy
Spinal Cord drug effects
Spinal Cord metabolism
Time Factors
Antigens, Surface therapeutic use
Cytokines metabolism
Hyperalgesia etiology
Inflammation etiology
Receptors, Cell Surface therapeutic use
Sciatica complications
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2094
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 26891688
- Full Text :
- https://doi.org/10.1186/s12974-016-0508-8