The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection

Wei, Xu-Hong; Na, Xiaodong; Liao, Guang-Jie; Chen, Qiuying; Chen, Yu; Chen, Fengying; Li, Yongyong; Zang, Ying; Liu, Xianguo

doi:10.1016/j.expneurol.2012.12.007

Cited by 89 publications

(79 citation statements)

References 52 publications

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“…Inhibition of TNF-a synthesis [36] and treatment with a TNF-a neutralizing antibody both attenuate the neuropathic pain induced by peripheral nerve injury [37]. The prevailing evidence shows that TNF-a stimulates IL-1b and IL-6 release from DRGs and the spinal cord following nerve injury [38,39]. Further, the spinal nerve ligation-induced increase in the expression of CXCL1 in the L5 spinal cord is regulated by TNF-a [19] and i.t.…”

Section: Tnf-a Might Mediate the Increased Cxcl12 Expression In The Dmentioning

confidence: 99%

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Bai

Wang

et al. 2016

Neurosci. Bull.

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Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mechanism. Here, we determined that spared nerve injury (SNI) increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia (DRG) neurons and satellite glial cells. SNI also induced longlasting upregulation of CXCL12 and CXCR4 in the ipsilateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNIinduced a sustained increase in TNF-a expression in the DRG and spinal cord. Intraperitoneal injection (i.p.) of the TNF-a synthesis inhibitor thalidomide reduced the SNI-induced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection (i.t.) of the CXCR4 antagonist AMD3100, both 30 min before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. administration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the activation of ERK in the spinal cord. The mechanical hypersensitivity induced in naïve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-a might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL12/CXCR4 signaling via ERK activation contributes to the development and maintenance of neuropathic pain.

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Section: Tnf-a Might Mediate the Increased Cxcl12 Expression In The Dmentioning

confidence: 99%

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Bai

Wang

et al. 2016

Neurosci. Bull.

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“…Immunofluorescence staining was performed following the procedures described by our previous works Wei et al, 2013a). Briefly, after defined survival times, rats were anesthetized and perfused with saline followed by 4% paraformaldehyde in 0.1 M phosphate buffer (PB).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…As described by our previous work (Wei et al, 2013a), the animals were decapitated after defined survival times, and the bilateral L4-L6 DRGs were removed and homogenated in Tris buffer at pH 7.6 containing a protease inhibitor cocktail (Roche Molecular Biochemicals, Indianapolis, IN). The total protein concentration in the samples was determined with the BCA protein assay (Pierce, Rockford IL).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Furthermore, pain also constitutes the major non motor syndrome in Parkinson's disease (PD) (Dieb et al, 2014;Pellaprat et al, 2014). In our recent work, we have found that L5-VRT up-regulates interleukin-6 (IL-6) in uninjured primary afferent system, and that the absence of IL-6 achieved by pre-treatment with IL-6 neutralizing antibody delays the induction of mechanical allodynia in bilateral hindpaws (Wei et al, 2013a). However, the upstream regulatory mechanisms underlying the IL-6 overexpression after motor fiber injury are still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons

Zang

Chen

Liao

et al. 2015

Brain, Behavior, and Immunity

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“…The dorsal spinal cord then acts as an important pain modulation center, as it provides a place for the brainstem descending suppression system to execute its action and also regulates the transmission of nociceptive information through the intermediate neurons (Singh and Tao 2012;Takazawa and MacDermott 2010;Yang and Ma 2011). Many studies have shown that a large amount of pain-associated molecules act in the dorsal spinal cord, especially those associated with nerve pathological pain (Quan-Xin et al 2012;Wei et al 2013;Xie et al 2012;Zhu et al 2013). Besides, various neurotransmitters and neurotransmitter receptors in the dorsal spinal cord could be altered during the nerve pathological pain (Paul et al 2012;Rahman et al 2007;Wan et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat dorsal spinal cord using differential proteomics

et al. 2015

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Chronic post-surgical pain (CPSP) is a normal and significant symptom in clinical surgery, such as breast operation, biliary tract operation, cesarean operation, uterectomy and thoracic operation. Severe chronic post-surgical pain could increase post-surgical complications, including myocardial ischemia, respiratory insufficiency, pneumonia and thromboembolism. However, the underlying mechanism is still unknown. Herein, a rat CPSP model was produced via thoracotomy. After surgery, in an initial study, 5 out of 12 rats after surgery showed a significant decrease in mechanical withdrawal threshold and/or increase in the number of acetone-evoked responses, and therefore classified as the CPSP group. The remaining seven animals were classified as non-CPSP. Subsequently, open-chest operation was performed on another 30 rats and divided into CPSP and non-CPSP groups after 21-day observation. Protein expression levels in the dorsal spinal cord tissue were determined by 12.5 % SDS-PAGE. Finally, differently expressed proteins were identified by LC MS/MS and analyzed by MASCOT software, followed by Gene Ontology cluster analysis using PANTHER software. Compared with the non-CPSP group, 24 proteins were only expressed in the CPSP group and another 23 proteins expressed differentially between CPSP and non-CPSP group. Western blot further confirmed that the expression of glutaminase 1 (GLS1) was significantly higher in the CPSP than in the non-CPSP group. This study provided a new strategy to identify the spinal proteins, which may contribute to the development of chronic pain using differential proteomics, and suggested that GLS1 may serve as a potential biomarker for CPSP.

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The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection

Cited by 89 publications

References 52 publications

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons

Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat dorsal spinal cord using differential proteomics

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