Effects of riluzole on P2X7R expression in the spinal cord in rat model of neuropathic pain

Jiang, Kai; Zhuang, Yi; Yan, Ming; Chen, Hui; Ge, Anqi; Sun, Li; Miao, Bei

doi:10.1016/j.neulet.2016.02.065

Cited by 26 publications

(13 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…showed downregulation of Slc47a2 in the thyroid tissue by oligonucleotide microarray, 24h after I-131 administration in rats [ 34 ]. Previous studies showed enhanced expression of P2×7R in the spinal cord dorsal horn in a rat model of neuropathic pain induced by chronic constriction injury [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts. The differentially expressed mRNAs were annotated as “biological process,” “cellular components” and “molecular functions” through gene ontology enrichment analysis. KEGG pathway enrichment analysis showed that cell cycle and renin-angiotensin pathways were upregulated in response to I/R, while protein digestion and absorption, hedgehog, neurotrophin, MAPK, and PI3K-Akt signaling were downregulated. The RNA-seq data was validated by qRT-PCR and western blot analyses of select mRNAs and lncRNAs. We observed that Bax, Caspase-3 and phospho-AKT were upregulated and Bcl-2 was downregulated in the spinal cord in response to renal injury. We also found negative correlations between three lncRNAs (TCONS_00042175, TCONS_00058568 and TCONS_00047728) and the degree of renal injury. These findings provide evidence for differential expression of lncRNAs and mRNAs in the lower thoracic spinal cord following I/R-induced AKI in rats and suggest potential clinical applicability.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that P2X 7 receptor (P2X 7 R) is involved in regulating inflammation and pain (15). Moreover, P2X 7 R upregulation in macrophages and P2X 7 R upregulation in spinal cord following peripheral nerve damage has been reported (16,17). Pain sensitivity has also been linked to P2X 7 R gene polymorphisms in women with post-mastectomy pain syndrome (PMPS) and OA (11,18,19).…”

Section: Introductionmentioning

confidence: 99%

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

Yang

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

P2X purinoceptor 7 (P2X7) receptor (P2X7R) is known to play a significant role in inflammation and pain-causing diseases, including osteoarthritis (OA). However, the mechanisms of action of P2X7R and its role in OA remain unclear. The articular cartilage is the crucial region in which pathological changes occur in OA, involving the dysregulation of degradation and maintenance mechanisms. In this study, we aimed to reveal the molecular mechanisms of action of P2X7R in articular cartilage in OA-induced pain and inflammation by using AZD9056, an antagonist of P2X7R. We created an animal model of OA by using Wistar rats administered (by intra-articular injection) monosodium iodoacetate (MIA), and the rats with OA were then treated with the P2X7R antagonist, AZD9056. We found that treatment with AZD9056 exerted pain-relieving and anti-inflammatory effects. Importantly, we found that the upregulated expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase-13 (MMP-13), substance P (SP) and prostaglandin E2 (PGE2) which was induced by MIA in cartilage tissues was reversed by AZD9056. Western blot analysis was used to examine the expression of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, inhibitor of NF-κB (IκB)α, NF-κB p65 and their phosphorylation forms; they were found to be significantly increased in the knee cartilage tissues from rats with OA; however, opposite effects were observed by the injection of AZD9056. These results implied that P2X7R was associated with the activation of the NF-κB pathway in the development of OA. Our results also revealed that helenalin, an NF-κB pathway inhibitor, decreased the expression of P2X7R, IL-1β, IL-6, TNF-α, SP, PGE2 and MMP-13, which was induced by MIA, in the knee cartilage tissues of rats with OA. On the whole, our findings suggest that P2X7R regulates the MMP-13 and NF-κB pathways in cartilage tissue and mediate OA-induced pain and inflammation.

show abstract

“…As the innate immune cell in the central nervous system, microglia marked by IBA-1 play a key role in mediating neuroinflammation after injury. P2X7R, a subtype of purine receptor, is distributed on various types of cell surfaces, including microglia in the central nervous system, and has important effects on many pathological reactions of neuroinflammation [ 21 , 22 ]. To determine the expression of P2X7R on spinal cord microglia after SCI, immunofluorescent staining was carried out to examine if there was P2X7R and IBA-1 double-positivity (P2X7R + /IBA-1 + ) cells in the spinal cord after SCI.…”

Section: Resultsmentioning

confidence: 99%

P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury

Fan

Zhang

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

Background Microglia participate in mediating neuroinflammation in which P2X7R triggered by adenosine triphosphate has a critical effect after spinal cord injury. However, how the P2X7R of microglia regulate neuroinflammation after spinal cord injury is still unclear. The aim of this study was to explore the mechanism by which the P2X7 receptor of microglia regulates neuroinflammation after spinal cord injury in NLRP3 inflammasome-dependent inflammation. Material/Methods Sixt rats were divided into 5 groups: a sham group, a model group, a BzATP group, an A-438079 group, and a BzATP+CY-09 group. Rats in the sham group were only subjected to laminectomy and rats in the other groups were subjected to spinal cord injury followed by treatment with physiological saline, BzATP, A-438079, and BzATP following CY-09, separately. Real-time polymerase chain reaction, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to analyze the scientific hypothesis. Results (i) P2X7R of microglia was upregulated and downregulated by BzATP, and A-438079 was upregulated after spinal cord injury. (ii) Upregulation of P2X7R on microglia is coincident with increase of neuroinflammation after spinal cord injury. (iii) P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation. Conclusions P2X7R of microglia in spinal cord mediates neuroinflammation by regulating NLRP3 inflammasome-dependent inflammation after spinal cord injury.

show abstract

Effects of riluzole on P2X7R expression in the spinal cord in rat model of neuropathic pain

Cited by 26 publications

References 37 publications

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury

Contact Info

Product

Resources

About