Antinociceptive effects of IL-6R vs. glucocorticoid receptors during rat hind paw inflammatory pain

Li, Xiongjuan; Wang, Weihong; Chen, Qionghui; Zhou, Yongchang; Wang, Lingzhi; Huang, Huansen

doi:10.1016/j.neulet.2020.135356

Cited by 11 publications

(11 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that local intraplantar injection of Dexa or Cane decreases the levels IL‐6, pJAK2, and pSTAT3 Ser727 proteins in the spinal cord (Figure 4), which did not decrease further by Dexa/Cane combination, suggesting crosstalk with the IL‐6/JAK2/STAT3 signaling pathway. This was in line with the crosstalk between GR and IL‐6R and shared the same downstream signaling pathway in the spinal cord 23 . We selected intraplantar delivery of Dexa and/or Cane in effective doses to the rats and determined the protein in the spinal cord in the present study, the reasons could be as follows.…”

Section: Discussionmentioning

confidence: 73%

“…This was in line with the crosstalk between GR and IL‐6R and shared the same downstream signaling pathway in the spinal cord. 23 We selected intraplantar delivery of Dexa and/or Cane in effective doses to the rats and determined the protein in the spinal cord in the present study, the reasons could be as follows. (1) Direct effect: local administration of steroid hormones that are absorbed into the blood and pass through the blood brain barrier into the central nervous system, 24 which may contribute to the reduction of cytokine levels by suppression of peripheral and central sensitization.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Liu

Xie

et al. 2022

Immunity Inflam & Disease

View full text Add to dashboard Cite

Background Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa‐ or Cane‐mediated nongenomic and genomic effects on mechanical nociception and inflammation‐induced changes in interleukin‐6 (IL‐6) mediated signaling pathway in rats. Methods Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague–Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL‐6, IL‐6Rα, JAK2, pJAK2, STAT3, pSTAT3Ser727, migration inhibitory factor, and cyclooxygenase‐2 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL‐6. The competition binding assay was carried out using enzyme‐linked immunosorbent assays (ELISA). Results Administration of Dexa and Cane dose‐dependently attenuated FCA‐induced inflammatory pain. The sub‐additive effect of Dexa/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL‐6, pJAK2, and pSTAT3Ser727. The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR138 binding site of IL‐6 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL‐6 than Cane. Conclusions There was no additive or negative effect of Dexa and Cane, and they modulate the IL‐6/JAK2/STAT3 signaling pathway through competitive binding with IL‐6 and relieves hypersensitivity during inflammatory pain.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Liu

Xie

et al. 2022

Immunity Inflam & Disease

View full text Add to dashboard Cite

show abstract

“…Nine URs met this criterion: Interleukin 6 Receptor (IL6R), Mitogen-activated Protein Kinase Kinase (MEK), Interleukin Enhancer-binding Factor 3 (ILF3), Runt-related Transcription Factor 2 (RUNX2), Protein Kinase AMP-Activated Catalytic Subunit Alpha 2 (PRKAA2) (UR was AMPKα2 gene), Follicle Stimulating Hormone (FSH), Activating Transcription Factor 4 (ATF4), Snail Family Transcriptional Repressor 1 (SNAI1), and Inhibin Subunit Alpha (INHA) ( Figure 3F ). Interestingly, pre-clinical and clinical literature supports a positive association between upregulation/activation of IL6R ( 62–64 ), MEK ( 65–67 ), RUNX2 ( 68, 69 ), FSH ( 70 ), & ATF4 ( 71, 72 ) and nociceptive states, and several laboratories have validated interventions in relevant pathways as promising anti-nociceptive therapeutic strategies. Only AMPKα2 activity was expressed towards a pro-nociceptive direction in this list, as pre-clinical literature suggests activation of this protein is associated with the alleviation of nociceptive symptoms ( 73, 74 ).These data suggest that other targets in this list may serve as novel therapeutic avenues of pain management.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model

Serafini¹,

Frere

Zimering

et al. 2022

Preprint

View full text Add to dashboard Cite

Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.

show abstract

“…IL-6, a proinflammatory cytokine, has various effects on the nervous system, involving neuroprotection, nerve regeneration and enhancement of nociception [ 38 ]. IL-6 can induce the dorsal root ganglion nociceptor excitability and interact with IL-6R to stimulate inflammatory processes [ 39 ]. IL-6 is also strongly and consistently associated with depression and anxiety [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology approach to predict potential targets and mechanisms of “Ramulus Cinnamomi (cassiae) – Paeonia lactiflora” herb pair in the treatment of chronic pain with comorbid anxiety and depression

Pan

Wei

et al. 2022

Annals of Medicine

View full text Add to dashboard Cite

Background Traditional Chinese medicine (TCM) prescriptions have multiple bioactive properties. “Gui Zhi–Shao Yao” herb pair is widely used to treat chronic pain (CP), as well as anxiety and depression. However, its related targets and underlying mechanisms have not been deciphered. Methods In this study, the network pharmacology method was used to explore the bioactive components and targets of “Gui Zhi–Shao Yao” herb pair and further elucidate its potential biological mechanisms of action in the treatment of CP with comorbid anxiety disorder (AD) and mental depression (MD). Results Following a series of analyses, we identified 15 active compounds, hitting 130 potential targets. After the intersections the targets of this herb pair and CP, AD and MD – sorted by the value of degree – nine targets were identified as the vital ones: Akt1, IL6, TNF, PTGS2, JUN, CASP3, MAPK8, PPARγ and NOS3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results demonstrated 11 pathways, such as AGE-RAGE signalling pathway, IL-17 signalling pathway, TNF signalling pathway, which primarily participate in the pathological processes. Conclusions This study preliminarily predicted and verified the pharmacological and molecular mechanisms of “Gui Zhi–Shao Yao” herb pair for treating CP with comorbid AD and MD from a holistic perspective. In vivo and in vitro experiments will be required to further investigate the mechanisms. KEY MESSAGE A network pharmacology approach was applied to identify key targets and molecular mechanisms. Nine targets were regarded as the vital targets for chronic pain with comorbid anxiety and depression. Predicted 11 pathways were the potential therapy targets and pharmacological mechanism of “Gui Zhi–Shao Yao” herb pair.

show abstract

Antinociceptive effects of IL-6R vs. glucocorticoid receptors during rat hind paw inflammatory pain

Cited by 11 publications

References 24 publications

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro

SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model

A network pharmacology approach to predict potential targets and mechanisms of “Ramulus Cinnamomi (cassiae) – Paeonia lactiflora” herb pair in the treatment of chronic pain with comorbid anxiety and depression

Contact Info

Product

Resources

About