Pharmacological Blockade of Spinal CXCL3/CXCR2 Signaling by NVP CXCR2 20, a Selective CXCR2 Antagonist, Reduces Neuropathic Pain Following Peripheral Nerve Injury

Piotrowska, Anna; Rojewska, Ewelina; Pawlik, Katarzyna; Kreiner, Grzegorz; Ciechanowska, A; Makuch, Wioletta; Nalepa, Irena; Mika, Joanna

doi:10.3389/fimmu.2019.02198

Cited by 28 publications

(63 citation statements)

References 111 publications

(147 reference statements)

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“…Other cytokines from our top DE gene list, such as CXCL1, 2 or 3 (all ligands of the CXCR2 receptor), have also been shown to be pro-nociceptive [ 51 ]. Intrathecal administration of CXCL1, 2 or 3 produced hyperalgesia in mice [ 52 ]. These chemokines have also been implicated in neuropathic pain [ 52 – 54 ] and nociceptive sensitization after traumatic brain injury [ 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

et al. 2021

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Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks. Methods Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit. Results We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks. Conclusions It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation.

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Section: Discussionmentioning

confidence: 99%

“…Intrathecal administration of CXCL1, 2 or 3 produced hyperalgesia in mice [ 52 ]. These chemokines have also been implicated in neuropathic pain [ 52 – 54 ] and nociceptive sensitization after traumatic brain injury [ 55 , 56 ]. CXCL1 in the synovial fluid of osteoarthritis patients correlated with the severity of pain [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

et al. 2021

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“…Liu found that CxCl3 was highly expressed in the cervical spinal cord of pruritus animal model, suggesting that CxCl3 may mediate pruritus [ 47 ]. In addition, Piotrowska proved that CXCL3 may mediate the process of neuropathic pain and hyperalgesia [ 48 ]. Consistent with these results, we found that PDYN and CXCL3 were differentially expressed in the DRG of PHN rats.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Genes and Mechanisms in Postherpetic Neuralgia

Qiu

Hao

Cheng

et al. 2020

Pain Research and Management

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Objective. Elderly patients are prone to postherpetic neuralgia (PHN), which may cause anxiety, depression, and sleep disorders and reduce quality of life. As a result, the life quality of patients was seriously reduced. However, the pathogenesis of PHN has not been fully elucidated, and current treatments remain inadequate. Therefore, it is important to explore the molecular mechanism of PHN. Methods. We analyzed the GSE64345 dataset, which includes gene expression from the ipsilateral dorsal root ganglia (DRG) of PHN model rats. Differentially expressed genes (DEGs) were identified and analyzed by Gene Ontology. Protein-protein interaction (PPI) network was constructed. The miRNA associated with neuropathic pain and inflammation was found in miRNet. Hub genes were identified and analyzed in Comparative Toxicogenomics Database (CTD). miRNA-mRNA networks associated with PHN were constructed. Results. A total of 116 genes were up-regulated in the DRG of PHN rats, and 135 genes were down-regulated. Functional analysis revealed that variations were predominantly enriched for genes involved in neuroactive ligand-receptor interactions, the Jak-STAT signaling pathway, and calcium channel activity. Eleven and thirty-one miRNAs associated with neuropathic pain and inflammation, respectively, were found. Eight hub genes (S1PR1, OPRM1, PDYN, CXCL3, S1PR5, TBX5, TNNI3, MYL7, PTGDR2, and FBXW2) associated with PHN were identified. Conclusions. Bioinformatics analysis is a useful tool to explore the mechanism and pathogenesis of PHN. The identified hub genes may participate in the onset and development of PHN and serve as therapeutic targets.

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“…Interestingly, CXCR2 antagonists have demonstrated an antinociceptive effect in the CCI model of NP [67]. Therefore, the femalespeci c upregulation of cxcr2 suggests that CXCR2 antagonists might be more e cacious for NP in females.…”

Section: Other Changes To the Immunological Responsementioning

confidence: 99%

Spared nerve injury causes sexually dimorphic mechanical allodynia and differential gene expression in spinal cords and dorsal root ganglia in rats

Ahlström

Mätlik

Viisanen

et al. 2020

Preprint

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BACKGROUND Neuropathic pain (NP) is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. Using the spared nerve injury (SNI) model in rats, we characterized sex differences in behaviour, analysed dorsal root ganglion (DRG) and spinal cord (SC) tissues with transcriptomics and immunohistochemistry assays, and examined the proteome of cerebrospinal fluid (CSF). METHODS The study comprised two experiments, with male and female Sprague-Dawley rats subjected to SNI- and sham-surgeries. Mechanical and cold allodynias were assessed using von Frey filaments and the acetone test, respectively. Samples were extracted on Day 21 for CSF proteome and DRG and SC analysis for neuronal markers (IB4 and CGRP) and glial cell markers (IBA1 and GFAP), respectively, in Experiment I. Lumbar 4-5 DRGs and SC segments were collected for RNA-seq analysis on Day 7 in Experiment II. Differential gene expression in DRG and SC was calculated using DESeq2, and pathway analyses were conducted using iPathwayguide. RESULTS Females developed stronger mechanical allodynia in both experiments. Equivalent decreases in CGRP and IB-4 positive cell counts in DRG and increases in glial cells markers in the SC were seen in both sexes. No CSF protein showed change following SNI in any group. RNASeq of DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). Analyses of biological processes revealed differences in T and B cell functions in DRG and neuronal processes in both DRG and SC. CONCLUSIONS We observed significantly stronger mechanical allodynia in females and many sexually dimorphic changes in gene expression, following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP and underline the importance of investigating NP in both sexes.

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Pharmacological Blockade of Spinal CXCL3/CXCR2 Signaling by NVP CXCR2 20, a Selective CXCR2 Antagonist, Reduces Neuropathic Pain Following Peripheral Nerve Injury

Cited by 28 publications

References 111 publications

Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

Bioinformatics Analysis of Genes and Mechanisms in Postherpetic Neuralgia

Spared nerve injury causes sexually dimorphic mechanical allodynia and differential gene expression in spinal cords and dorsal root ganglia in rats

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