Diabetes-induced Neuropathic Mechanical Hyperalgesia Depends on P2X4 Receptor Activation in Dorsal Root Ganglia

Teixeira, Juliana Maia; Santos, Gilson Gonçalves dos; Neves, Amanda Ferreira; Athié, Maria Carolina Pedro; Bonet, Ivan José Magayewski; Nishijima, Catarine Massucato; Farias, Felipe Hertzing; Figueiredo, Jozi Godoy; Hernández‐Olmos, Víctor; Alshaibani, Samer; Tambeli, Cláudia Herrera; Müller, Christa E.; Parada, Carlos Amílcar

doi:10.1016/j.neuroscience.2018.12.003

Cited by 42 publications

(27 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[8,9]. Consistent with previous study, the expression of spinal P2X 4 R was up-regulated in SNI rats and DNP rats [29][30][31]. Additionally, P2X 4 R was mostly expressed in microglial cell [32,33].…”

Section: Discussionsupporting

confidence: 84%

MiR-106b-5p represses neuropathic pain by regulating P2X4 receptor in the spinal cord in mice

Tan

Wei

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: P2X4 receptor (P2X4R)-mediated spinal microglial activation makes a critical contribution to pathologically enhanced pain processing in the dorsal horn. It can be upregulated under conditions of neuropathic pain. However, the specific mechanism of pathogenesis and potential molecular targets has not yet been made explicit. MicroRNAs (miRNAs) are commonly recognized as indicators in neuropathic pain pathophysiology.Methods: We established the pain model of spared nerve injury (SNI), and the 50% paw withdrawal thresholds (PWMTs) were used to assess behavior of mouse. MiRNA expression profiling was performed to detect differential expressed miRNA. The western-bolt and quantitative real time PCR to examine P2X4R and miRNA expression in the mouse. Dual-luciferase reporter assays confirmed the correlation between P2X4R and miRNA. Fluorescence in situ hybridization was used to show location between P2X4R and miRNA. Results: In the present study, we found that P2X4R was up-regulated in the spinal dorsal horn of mice following spared nerve injury (SNI), and we identified 69 miRNAs (46 up-regulated and 23 down-regulated miRNAs) were differently expressed (fold change > 2, P < 0.05). P2X4R was a major target of miR-106b-5p (one of down-regulated miRNAs in SNI) with bioinformatics technology and quantitative real time PCR analysis validated the expressed change of miR-106b-5p, and dual-luciferase reporter assays confirmed the correlation between them. Fluorescence in situ hybridization showed that miR-106b-5p was co-localized with P2X4R in the spinal cord. Transfection with miR-106b-5p mimic on BV2 cells reversed the up-regulation of P2X4R induced by LPS. Moreover, miR-106b-5p overexpression significantly attenuated neuropathic pain induced by SNI, with decreased expression of P2X4R mRNA and protein in the spinal cord.Conclusion: Taken together, our results suggest that miR-106b-5p can serve as an important regulator of neuropathic pain development by targeting P2X4R.

show abstract

Section: Discussionsupporting

confidence: 84%

MiR-106b-5p represses neuropathic pain by regulating P2X4 receptor in the spinal cord in mice

Tan

Wei

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, BzATP is a potent agonist of other P2XRs (ref. 114 ), particularly P2X4R, and indeed there is evidence that P2X4R is upregulated in SGCs in the STZ model and that it is essential for the mechanical hypersensitivity observed in this model 115 . This topic needs to be further explored, particularly from the perspective of the degree to which SGC–neuron interaction is compromised and whether Cx43 or Panx1 is involved in the heightened P2R sensitivity in SGCs.…”

Section: Sgcs In Selected Pain Conditionsmentioning

confidence: 82%

Emerging importance of satellite glia in nervous system function and dysfunction

2020

View full text Add to dashboard Cite

Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic protein, stronger gap junction-mediated SGC–SGC and neuron–SGC coupling, increased sensitivity to ATP, downregulation of Kir4.1 potassium channels and increased cytokine synthesis and release. There is evidence that these changes in SGCs contribute to chronic pain by augmenting neuronal activity and that these changes are consistent in various rodent pain models and likely also in human pain. Therefore, understanding these changes and the resulting abnormal interactions of SGCs with sensory neurons could provide a mechanistic approach that might be exploited therapeutically in alleviation and prevention of pain. We describe how SGCs are altered in rodent models of four common types of pain: systemic inflammation (sickness behaviour), post-surgical pain, diabetic neuropathic pain and post-herpetic pain.

show abstract

“…The existence of functional P2X7 receptors was confirmed here by the activating effect of BzATP, the high affinity P2X7R agonist [ 12 ], which was here more effective than 100 µM ATP. However, BzATP was as effective as ATP to evoke currents at 3–30 µM, which may be explained by the nonspecific effect of BzATP, which activates P2X7 but also P2X4 receptors [ 42 , 63 , 64 ]. Alternatively, BzATP may activate the P2X7R via its high affinity ATP activation site, which has an EC 50 for ATP similar to the P2X4R [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Dissection of P2X4 and P2X7 Receptor Current Components in BV-2 Microglia

Trang

Schmalzing

Müller

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Microglia cells represent the immune system of the central nervous system. They become activated by ATP released from damaged and inflamed tissue via purinergic receptors. Ionotropic purinergic P2X4 and P2X7 receptors have been shown to be involved in neurological inflammation and pain sensation. Whether the two receptors assemble exclusively as homotrimers or also as heterotrimers is still a matter of debate. We investigated the expression of P2X receptors in BV-2 microglia cells applying the whole-cell voltage-clamp technique. We dissected P2X4 and P2X7 receptor-mediated current components by using specific P2X4 and P2X7 receptor blockers and by their characteristic current kinetics. We found that P2X4 and P2X7 receptors are activated independently from each other, indicating that P2X4/P2X7 heteromers are not of functional significance in these cells. The pro-inflammatory mediators lipopolysaccharide and interferon γ, if applied in combination, upregulated P2X4, but not P2X7 receptor-dependent current components also arguing against phenotypically relevant heteromerization of P2X4 and P2X7 receptor subunits.

show abstract

Diabetes-induced Neuropathic Mechanical Hyperalgesia Depends on P2X4 Receptor Activation in Dorsal Root Ganglia

Cited by 42 publications

References 63 publications

MiR-106b-5p represses neuropathic pain by regulating P2X4 receptor in the spinal cord in mice

MiR-106b-5p represses neuropathic pain by regulating P2X4 receptor in the spinal cord in mice

Emerging importance of satellite glia in nervous system function and dysfunction

Dissection of P2X4 and P2X7 Receptor Current Components in BV-2 Microglia

Contact Info

Product

Resources

About