The major histocompatibility complex genes impact pain response in DA and DA.1U rats

Guo, Yuan; Yao, Fanrong; Cao, Dong-Yuan; Li, Li; Xie, Wen; Zhao, Yan

doi:10.1016/j.physbeh.2015.04.009

Cited by 4 publications

(6 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, nerve injury increases the activity of Hdac1 and Ezh2 (Laumet et al, 2015 ). Pain responses depend on genes from the major histocompatibility complex (MHC; Guo et al, 2015 ), and the MHC-2 haplotype is involved in the incidence of postherpetic pain (Sato-Takeda et al, 2006 ). Further, MHC-2 molecules synergize with Toll-like receptor Tlr4 in inducing an innate immune response (Frei et al, 2010 ), and the lymphocyte antigen Ly86 is required in DRG neurons for functional Toll-like receptor Tlr4 signaling (Grace et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Kummer

Kalpachidou

Kress

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Fabry disease is an X-linked lysosomal storage disorder with involvement of the nervous system. Accumulation of glycosphingolipids within peripheral nerves and/or dorsal root ganglia results in pain due to small-fiber neuropathy, which affects the majority of patients already in early childhood. The α-galactosidase A deficient mouse proved to be an adequate model for Fabry disease, as it shares many symptoms including altered temperature sensitivity and pain perception. To characterize the signatures of gene expression that might underlie Fabry disease-associated sensory deficits and pain, we performed one-color based hybridization microarray expression profiling of DRG explants from adult α-galactosidase A deficient mice and age-matched wildtype controls. Protein-protein interaction (PPI) and pathway analyses were performed for differentially regulated mRNAs. We found 812 differentially expressed genes between adult α-galactosidase A deficient mice and age-matched wildtype controls, 506 of them being upregulated, and 306 being downregulated. Among the enriched pathways and processes, the disease-specific pathways “lysosome” and “ceramide metabolic process” were identified, enhancing reliability of the current analysis. Novel pathways that we identified include “G-protein coupled receptor signaling” and “retrograde transport” for the upregulated genes. From the analysis of downregulated genes, immune-related pathways, autoimmune, and infection pathways emerged. The current analysis is the first to present a differential gene expression profile of DRGs from α-galactosidase A deficient mice, thereby providing knowledge on possible mechanisms underlying neuropathic pain related symptoms in Fabry patients. Therefore, the presented data provide new insights into the development of the pain phenotype and might lead to new treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Kummer

Kalpachidou

Kress

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In addition, an MHC haplotype involved in the incidence of post-herpetic pain has also been reported (Sato-Takeda et al, 2006). More recently, another group found that MHC II contributes to differences in basal pain sensitivity and nociceptive responses in a formalin-induced pain model (Guo et al, 2010(Guo et al, , 2015. However, MHC II has yet to be linked to BCP.…”

Section: Discussionmentioning

confidence: 97%

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

Song

Xiong

Zheng

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Major histocompatibility class II (MHC II)-specific activation of CD4 T helper cells generates specific and persistent adaptive immunity against tumors. Emerging evidence demonstrates that MHC II is also involved in basic pain perception; however, little is known regarding its role in the development of cancer-induced bone pain (CIBP). In this study, we demonstrate that MHC II expression was markedly induced on the spinal microglia of CIBP rats in response to STAT1 phosphorylation. Mechanical allodynia was ameliorated by either pharmacological or genetic inhibition of MHC II upregulation, which was also attenuated by the inhibition of pSTAT1 and pERK but was deteriorated by intrathecal injection of IFNγ. Furthermore, inhibition of ERK signaling decreased the phosphorylation of STAT1, as well as the production of MHC II in vivo and in vitro. These findings suggest that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia.

show abstract

“…The method of immunohistochemistry was detailed in our recent publication . Briefly, the rats were anaesthetized and perfused by 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…The method of immunohistochemistry was detailed in our recent publication. 6,7 Briefly, the rats were anaesthetized and perfused by 4% paraformaldehyde. The L4/L5 spinal cord segments were post-fixed, and cryoprotected in 30% sucrose.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…It is notable that the MHC genes of DA rats are connected with mechanical hypersensitivity . A recent study by the authors showed that DA rats were more sensitive in basal pain sensitivity and formalin pain model, and that the MHC molecular RT1‐B might be involved in the process . However, the difference of pain sensitivity in arthritis between the two strains is unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats

Yao

Wang

Zhao

2016

Clin Exp Pharma Physio

Self Cite

View full text Add to dashboard Cite

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

show abstract

The major histocompatibility complex genes impact pain response in DA and DA.1U rats

Cited by 4 publications

References 55 publications

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats

Contact Info

Product

Resources

About