RGD Reference Report - Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. - Rat Genome Database

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Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats.

Authors: Kuang, X  Huang, Y  Gu, HF  Zu, XY  Zou, WY  Song, ZB  Guo, QL 
Citation: Kuang X, etal., Eur J Pharmacol. 2012 Feb 15;676(1-3):51-6. doi: 10.1016/j.ejphar.2011.11.037. Epub 2011 Dec 7.
RGD ID: 7364836
Pubmed: PMID:22173123   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2011.11.037   (Journal Full-text)

Numerous studies revealed that spinal inflammation and immune response play an important role in neuropathic pain. In this study, we investigated the effects of intrathecal injection of a Toll-like receptor (TLR4) inhibitor epigallocatechin gallate (EGCG) on neuropathic pain induced by chronic constriction injury of the sciatic nerve (CCI). A total of 120 rats were randomly assigned into 4 groups: sham-operated group, CCI group, CCI plus normal saline group and CCI plus EGCG group. CCI and sham surgeries were performed and both thermal hyperalgesia and mechanical allodynia were tested. Lumbar spinal cord was sampled and the mRNA and protein expressions of TLR4 and High Mobility Group 1 protein (HMGB1) were detected, the contents of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) were measured by ELISA, and immunohistochemistry for nuclear factor kappa B (NF-kappaB) was also carried out. When compared with the sham group, both mechanical and heat pain thresholds were significantly decreased, and the mRNA and protein expressions of TLR4 and HMGB1, the contents of TNF-alpha, IL-1beta and IL-10 in the spinal cords and NF-kappaB expression in the spinal dorsal horn were markedly increased in CCI rats (P<0.05). After intrathecal injection of EGCG (1mg/kg) once daily from 1day before to 3days after CCI surgery, the expressions of TLR4, NF-kappaB, HMGB1, TNF-alpha and IL-1beta were markedly decreased while the content of IL-10 in the spinal cord increased significantly accompanied by dramatical improvement of pain behaviors in CCI rats (P<0.05). These results show that the TLR4 signaling pathway plays an important role in the occurrence and development of neuropathic pain, and the therapy targeting TLR4 might be a novel strategy in the treatment of neuropathic pain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sciatic neuropathy treatmentISOIl10 (Rattus norvegicus)7364836; 7364836 RGD 
sciatic neuropathy treatmentISOIl1b (Rattus norvegicus)7364836; 7364836 RGD 
sciatic neuropathy treatmentIEP 7364836; 7364836; 7364836 RGD 
sciatic neuropathy  ISOTlr4 (Rattus norvegicus)7364836; 7364836mRNA and protein:increased expression:spinal cord:RGD 
sciatic neuropathy treatmentISOTnf (Rattus norvegicus)7364836; 7364836 RGD 
sciatic neuropathy  IEP 7364836mRNA and protein:increased expression:spinal cord:RGD 
sciatic neuropathy  IMP 7364836 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)
Il1b  (interleukin 1 beta)
Tlr4  (toll-like receptor 4)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Il10  (interleukin 10)
Il1b  (interleukin 1 beta)
Tlr4  (toll-like receptor 4)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
IL10  (interleukin 10)
IL1B  (interleukin 1 beta)
TLR4  (toll like receptor 4)
TNF  (tumor necrosis factor)


Additional Information