The Chemokine CXCL1/Growth Related Oncogene Increases Sodium Currents and Neuronal Excitability in Small Diameter Sensory Neurons

Wang, Jungang; Strong, Judith A.; Xie, Wenrui; Yang, Rui; Coyle, Dennis E.; Wick, Dayna M; Dorsey, Ericka D; Zhang, Junming

doi:10.1186/1744-8069-4-38

Cited by 90 publications

(92 citation statements)

References 36 publications

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“…Considerable data support the hypothesis that proinflammatory chemokines induce pain hypersensitivity, notably by causing sensory neuron hyperactivity (Wang et al, 2008;Miller et al, 2009;White et al, 2009). Accordingly, the intraganglionic release of CCL2 strongly excites CCR2-expressing nociceptive DRG neurons (Oh et al, 2001;White et al, 2005;Sun et al, 2006;Jung et al, 2008).…”

Section: Discussionmentioning

confidence: 77%

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Belkouch¹,

Dansereau²,

Goazigo³

et al. 2011

J. Neurosci.

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Changes in function of voltage-gated sodium channels in nociceptive primary sensory neurons participate in the development of peripheral hyperexcitability that occurs in neuropathic and inflammatory chronic pain conditions. Among them, the tetrodotoxin-resistant (TTX-R) sodium channel Na v 1.8, primarily expressed by small-and medium-sized dorsal root ganglion (DRG) neurons, substantially contributes to the upstroke of action potential in these neurons. Compelling evidence also revealed that the chemokine CCL2 plays a critical role in chronic pain facilitation via its binding to CCR2 receptors. In this study, we therefore investigated the effects of CCL2 on the density and kinetic properties of TTX-R Na v 1.8 currents in acutely small/medium dissociated lumbar DRG neurons from naive adult rats. Whole-cell patch-clamp recordings demonstrated that CCL2 concentration-dependently increased TTX-resistant Na v 1.8 current densities in both small-and medium-diameter sensory neurons. Incubation with CCL2 also shifted the activation and steady-state inactivation curves of Na v 1.

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Section: Discussionmentioning

confidence: 77%

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Belkouch¹,

Dansereau²,

Goazigo³

et al. 2011

J. Neurosci.

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“…The relative amount of the specific mRNA was normalized to the housekeeping gene hypoxanthine ribosyltransferase (14). The primers used for the identification of voltage-gated sodium channels were designed as described previously in the literature (Table 1) (40). Care was also taken to avoid regions of homology with other Na channels.…”

Section: Methodsmentioning

confidence: 99%

“…Real-time PCR was performed to investigate the mRNA expression of Na v s in renal and nonrenal neurons. The primers were used as described in the literature (40). DiD labeling identified renal neurons.…”

Section: Labeled Cells In Situ and In Culturementioning

confidence: 99%

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

Freisinger

Schatz

Ditting

et al. 2013

American Journal of Physiology-Renal Physiology

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Freisinger W, Schatz J, Ditting T, Lampert A, Heinlein S, Lale N, Schmieder R, Veelken R. Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels? Am J Physiol Renal Physiol 304: F491-F497, 2013. First published January 2, 2013; doi:10.1152/ajprenal.00011.2012.-Sensory neurons with afferent axons from the kidney are extraordinary in their response to electrical stimulation. More than 50% exhibit a tonic firing pattern, i.e., sustained action potential firing throughout depolarizing, pointing to an increased excitability, whereas nonrenal neurons show mainly a phasic response, i.e., less than five action potentials. Here we investigated whether these peculiar firing characteristics of renal afferent neurons are due to differences in the expression of voltage-gated sodium channels (Na vs). Dorsal root ganglion (DRG) neurons from rats were recorded by the current-clamp technique and distinguished as "tonic" or "phasic. .67]; P Ͻ 0.05). These findings point to an increased presence of the TTX-resistant Na vs 1.8 and 1.9. Furthermore, tonic neurons exhibited a relatively higher portion of TTX-resistant sodium currents. Interestingly, mRNA expression of TTX-resistant sodium channels was significantly increased in renal, predominantly tonic, DRG neurons. Hence, under physiological conditions, renal sensory neurons exhibit predominantly a firing pattern associated with higher excitability. Our findings support that this is due to an increased expression and activation of TTX-resistant Na vs.

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“…Inflammation and angiogenesis are necessary steps for healing; however, unbalanced angiogenesis/inflammation as a consequence of deregulation of the cytokine (chemokine) network can result in a chronic pathological environment that leads to impaired healing [28], often clinically manifested as pain. Prototypical inflammatory mediators such as interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1/ CCL2, IL-8/CXCL8, and IL-6/CXCL6 have been shown to induce acute or short-term hyperalgesia and are implicated directly in neuropathic pain, chronic hyperalgesia, and allodynia [37,39,40].…”

Section: Introductionmentioning

confidence: 99%

Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

Andı́a

Rubio‐Azpeitia

Maffulli

2015

Clinical Orthopaedics &Amp; Related Research

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Background Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. Questions/purposes The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes. Methods Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasmainduced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample. Results In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005-0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27-0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007-0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3-0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5-0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2-0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7-2.3; p \ 0.001). RANTES/CCL5 increased by10-fold (95% CI, 4-17) and hepatocyte growth factor by 21-fold (95% CI, 0.2-42) in tendinopathic and by 2.3-fold (95% CI, 2-3) and threefold (95% CI, 1-5) in normal cells (p = 0.005 for both). Conclusions Platelet-rich plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells. Clinical Relevance Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.

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The Chemokine CXCL1/Growth Related Oncogene Increases Sodium Currents and Neuronal Excitability in Small Diameter Sensory Neurons

Cited by 90 publications

References 36 publications

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

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The Chemokine CXCL1/Growth Related Oncogene Increases Sodium Currents and Neuronal Excitability in Small Diameter Sensory Neurons

Cited by 90 publications

References 36 publications

The Chemokine CCL2 Increases Nav1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Nav1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

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The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism