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

Abstract

BackgroundInteraction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases.MethodsImmunofluorescence 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.ResultsSeven 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.ConclusionsIntrathecal 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.

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion

“…We thus further explored the glial localization of CXCL10 in the spinal cord through double immunofluorescence staining. The enlarged area and strength of the immunostaining determined through the image analysis corresponded well with the sites showing activated microglia and astrocytes after injury [17,18]. As previously described, spinal glial activation can be determined by measuring Iba-1 (microglia) and GFAP (astrocytes) immunoreactivity [14].…”

“…Because glial cells are the main effectors and regulators of the spinal cord, activated populations of glial cells could produce a wide variety of proinflammatory cytokines that strongly affect the pathogenesis of sensory hypersensitivity [6,8,17,22]. Among these cytokines, TNF-α and IL-6 are known to function as potent proinflammatory cytokines during the reperfusion period [6,27,28].…”

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

“…Knowing that microglia activation and subsequent proinflammatory cytokine expression are responsible for enhanced pain hypersensitivity [32], we used Iba-1 as the microglial activation marker to see whether PF played a role in the activation of spinal microglia in the CFA-induced inflammatory pain mice. It was found that the fluorescence intensity in the spinal cord dorsal horn of CFA-injected mice was increased by more than 50% compared with that in Sham group, and the expression of Iba-1 was reduced after PF treatment (Fig.…”

Neuroimmunological mechanisms of chronic pain syndrome

“…Существуют иммунологические механизмы развития ПНБ, которые запускаются воспалительной реакцией и активаци-ей глиальных клеток в соответствующих сегментах спинно-го мозга [31,32].…”

“…Экспериментальные исследования показали, что инт-ратекальное введение крысам CD200R1 вызывает у них бы-строе ослабление глиальной активации и синтеза провоспа-лительных цитокинов спинного мозга, что приводит к уменьшению невропатической боли после эксперименталь-ного повреждения нерва [31].…”