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CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model.

Hernangómez M, Klusáková I, Joukal M, Hradilová-Svíženská I, Guaza C, Dubový P - J Neuroinflammation (2016)

Bottom Line: Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels.The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application.Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development.

View Article: PubMed Central - PubMed

Affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. mirihh@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Results of behavioral tests. Mechanical (a) and thermal hypersensitivity (b) in sCCI-operated rats treated with ACSF or CD200Fc. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were significantly decreased in the ipsilateral hind paws following sCCI when compared with 1 day before surgery, and CD200Fc treatment for 5 h was able to reverse these. Both behavioral signs of PNP were nevertheless significantly weaker 24 h from CD200Fc application, although they remained still higher than 7 days after sCCI operation but before CD200Fc application. All values in a and b represent mean ± SE from six rats per group. Asterisk indicates statistically significant difference (p < 0.001) when compared with measurements 1 day before operation; Plus sign indicates statistical significant difference (p < 0.01) when compared to values of sCCI-operated animals before and after CD200Fc application. Kruskal-Wallis ANOVA followed by Mann-Whitney U test.
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Fig1: Results of behavioral tests. Mechanical (a) and thermal hypersensitivity (b) in sCCI-operated rats treated with ACSF or CD200Fc. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were significantly decreased in the ipsilateral hind paws following sCCI when compared with 1 day before surgery, and CD200Fc treatment for 5 h was able to reverse these. Both behavioral signs of PNP were nevertheless significantly weaker 24 h from CD200Fc application, although they remained still higher than 7 days after sCCI operation but before CD200Fc application. All values in a and b represent mean ± SE from six rats per group. Asterisk indicates statistically significant difference (p < 0.001) when compared with measurements 1 day before operation; Plus sign indicates statistical significant difference (p < 0.01) when compared to values of sCCI-operated animals before and after CD200Fc application. Kruskal-Wallis ANOVA followed by Mann-Whitney U test.

Mentions: As CD200Fc appears to be beneficial when administered in cases of various diseases with an inflammatory component [34, 36, 40], we investigated whether the CD200R1 agonist has effects on PNP behavioral signs in the sCCI model. No statistically significant changes of thresholds and withdrawal latencies were measured in the hind paws of naïve rats treated with CD200Fc for 5 and 24 h, thus indicating no influence of the CD200R agonist on basal sensitivity (data not shown). Sham-operated rats displayed a small but not statistically significant mechanical and thermal hypersensitivity at days 1 and 3 with no behavioral changes after 7 days and ACSF treatment for 5 or 24 h (Fig. 1a, b). All hind paws of rats subjected to sCCI of the sciatic nerve displayed significantly decreased thresholds of mechanical (Fig. 1a) and withdrawal latencies of thermal hypersensitivity (Fig. 1b) at days 1, 3, and 7 post-operation when compared with 1 day before operation.Fig. 1


CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model.

Hernangómez M, Klusáková I, Joukal M, Hradilová-Svíženská I, Guaza C, Dubový P - J Neuroinflammation (2016)

Results of behavioral tests. Mechanical (a) and thermal hypersensitivity (b) in sCCI-operated rats treated with ACSF or CD200Fc. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were significantly decreased in the ipsilateral hind paws following sCCI when compared with 1 day before surgery, and CD200Fc treatment for 5 h was able to reverse these. Both behavioral signs of PNP were nevertheless significantly weaker 24 h from CD200Fc application, although they remained still higher than 7 days after sCCI operation but before CD200Fc application. All values in a and b represent mean ± SE from six rats per group. Asterisk indicates statistically significant difference (p < 0.001) when compared with measurements 1 day before operation; Plus sign indicates statistical significant difference (p < 0.01) when compared to values of sCCI-operated animals before and after CD200Fc application. Kruskal-Wallis ANOVA followed by Mann-Whitney U test.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4759712&req=5

Fig1: Results of behavioral tests. Mechanical (a) and thermal hypersensitivity (b) in sCCI-operated rats treated with ACSF or CD200Fc. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were significantly decreased in the ipsilateral hind paws following sCCI when compared with 1 day before surgery, and CD200Fc treatment for 5 h was able to reverse these. Both behavioral signs of PNP were nevertheless significantly weaker 24 h from CD200Fc application, although they remained still higher than 7 days after sCCI operation but before CD200Fc application. All values in a and b represent mean ± SE from six rats per group. Asterisk indicates statistically significant difference (p < 0.001) when compared with measurements 1 day before operation; Plus sign indicates statistical significant difference (p < 0.01) when compared to values of sCCI-operated animals before and after CD200Fc application. Kruskal-Wallis ANOVA followed by Mann-Whitney U test.
Mentions: As CD200Fc appears to be beneficial when administered in cases of various diseases with an inflammatory component [34, 36, 40], we investigated whether the CD200R1 agonist has effects on PNP behavioral signs in the sCCI model. No statistically significant changes of thresholds and withdrawal latencies were measured in the hind paws of naïve rats treated with CD200Fc for 5 and 24 h, thus indicating no influence of the CD200R agonist on basal sensitivity (data not shown). Sham-operated rats displayed a small but not statistically significant mechanical and thermal hypersensitivity at days 1 and 3 with no behavioral changes after 7 days and ACSF treatment for 5 or 24 h (Fig. 1a, b). All hind paws of rats subjected to sCCI of the sciatic nerve displayed significantly decreased thresholds of mechanical (Fig. 1a) and withdrawal latencies of thermal hypersensitivity (Fig. 1b) at days 1, 3, and 7 post-operation when compared with 1 day before operation.Fig. 1

Bottom Line: Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels.The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application.Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development.

View Article: PubMed Central - PubMed

Affiliation: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. mirihh@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus