Dataset Information

Spinal CXCL9 and CXCL11 are not involved in neuropathic pain despite an upregulation in the spinal cord following spinal nerve injury.

ABSTRACT: Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10, and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL) and acts on chemokine receptor CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known about CXCL9 and CXCL11 in the maintenance of neuropathic pain. Here, we report that CXCL9 and CXCL11, same as CXCL10, were increased in spinal astrocytes after SNL. Surprisingly, inhibition of CXCL9 or CXCL11 by spinal injection of shRNA lentivirus did not attenuate SNL-induced neuropathic pain. In addition, intrathecal injection of CXCL9 and CXCL11 did not produce hyperalgesia or allodynia behaviors, and neither of them induced ERK activation, a marker of central sensitization. Whole-cell patch clamp recording on spinal neurons showed that CXCL9 and CXCL11 enhanced both excitatory synaptic transmission and inhibitory synaptic transmission, whereas CXCL10 only produced an increase in excitatory synaptic transmission. These results suggest that, although the expression of CXCL9 and CXCL11 are increased after SNL, they may not contribute to the maintenance of neuropathic pain.

SUBMITTER: Wu XB

PROVIDER: S-EPMC5967156 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spinal CXCL9 and CXCL11 are not involved in neuropathic pain despite an upregulation in the spinal cord following spinal nerve injury.

Wu Xiao-Bo XB He Li-Na LN Jiang Bao-Chun BC Shi Hui H Bai Xue-Qiang XQ Zhang Wen-Wen WW Gao Yong-Jing YJ

Molecular pain 20180101

Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10, and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL) and acts on chemokine receptor CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known abo ...[more]

PMID: 29712506

Similar Datasets

Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).

Dataset Information

Spinal CXCL9 and CXCL11 are not involved in neuropathic pain despite an upregulation in the spinal cord following spinal nerve injury.

Publications

Spinal CXCL9 and CXCL11 are not involved in neuropathic pain despite an upregulation in the spinal cord following spinal nerve injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure