Differential lumbar spinal cord responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic painReport as inadecuate




Differential lumbar spinal cord responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic pain - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 8:88

First Online: 18 December 2012Received: 16 October 2012Accepted: 14 December 2012

Abstract

BackgroundOur previous studies have indicated that both lumbar spinal cord-infiltrating CD4 T cells and microglial CD40 contribute to the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain spinal nerve L5 transection L5Tx. To further delineate the CD4 and CD40-mediated mechanisms involved in the development of L5Tx-induced neuropathic pain behaviors, we examined the lumbar spinal cord mononuclear cells of wild type WT BALB-c, BALB-c-CD4 knockout KO, and BALB-c-CD40 KO mice via flow cytometry.

ResultsIn WT mice, L5Tx induced significant but transient at day 3 and-or day 7 increases of the total numbers of mononuclear cells, microglial cells CD45CD11b, and infiltrating leukocytes CD45 in the ipsilateral side of the spinal cord. In CD4 KO mice, significant elevation of microglia was detected only on day 7 post-L5Tx, while no significant increase in infiltrating leukocytes post-L5Tx was observed. CD40 KO mice did not exhibit any of the changes observed in WT mice. Furthermore, neutralizing CD40 antibody treatment indicated an early involvement of CD40 signaling in the development of L5Tx-induced mechanical hypersensitivity.

ConclusionsAltogether, data indicate that both CD4 and CD40 play a role in L5Tx-induced leukocyte infiltration into the lumbar spinal cord but have differential contributions to spinal cord microglial activation following peripheral nerve injury.

KeywordsNeuopathic pain Nerve injury CD4 T cells CD40 Microglia AbbreviationsANOVAAnalyses of variance

CNSCentral nervous system

IACUCInstitutional Animal Care and Use Committee

i.t.Intrathecal

IP-10Interferon gamma-induced protein 10

KOKnockout

L5TxSpinal nerve L5 transection

MCP-1Monocyte chemoattractant protein-1

mAbsMonoclonal antibodies

NCINational Cancer Institute

RANTESRegulated and normal T cell expressed and secreted

RMRepeated measures

SNKStudent-Newman-Keuls

TNFTumor necrosis factor

UNEUniversity of New England

WTWide type.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-88 contains supplementary material, which is available to authorized users.

Holly Beaulac and Adriana Eurich contributed equally to this work.

Download fulltext PDF



Author: Ling Cao - Holly Beaulac - Adriana Eurich

Source: https://link.springer.com/







Related documents