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Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats.
Eur J Pharmacol. 2012 Feb 15; 676(1-3):51-6.EJ

Abstract

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-α), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) were measured by ELISA, and immunohistochemistry for nuclear factor kappa B (NF-κB) 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-α, IL-1β and IL-10 in the spinal cords and NF-κB 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-κB, HMGB1, TNF-α and IL-1β 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.

Authors+Show Affiliations

Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, Hunan Province 410008, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22173123

Citation

Kuang, Xin, et al. "Effects of Intrathecal Epigallocatechin Gallate, an Inhibitor of Toll-like Receptor 4, On Chronic Neuropathic Pain in Rats." European Journal of Pharmacology, vol. 676, no. 1-3, 2012, pp. 51-6.
Kuang X, Huang Y, Gu HF, et al. Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. Eur J Pharmacol. 2012;676(1-3):51-6.
Kuang, X., Huang, Y., Gu, H. F., Zu, X. Y., Zou, W. Y., Song, Z. B., & Guo, Q. L. (2012). Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. European Journal of Pharmacology, 676(1-3), 51-6. https://doi.org/10.1016/j.ejphar.2011.11.037
Kuang X, et al. Effects of Intrathecal Epigallocatechin Gallate, an Inhibitor of Toll-like Receptor 4, On Chronic Neuropathic Pain in Rats. Eur J Pharmacol. 2012 Feb 15;676(1-3):51-6. PubMed PMID: 22173123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. AU - Kuang,Xin, AU - Huang,Yan, AU - Gu,Hong-Feng, AU - Zu,Xu-Yu, AU - Zou,Wang-Yuan, AU - Song,Zong-Bin, AU - Guo,Qu-Lian, Y1 - 2011/12/07/ PY - 2011/06/21/received PY - 2011/11/21/revised PY - 2011/11/27/accepted PY - 2011/12/17/entrez PY - 2011/12/17/pubmed PY - 2012/5/19/medline SP - 51 EP - 6 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 676 IS - 1-3 N2 - 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-α), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) were measured by ELISA, and immunohistochemistry for nuclear factor kappa B (NF-κB) 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-α, IL-1β and IL-10 in the spinal cords and NF-κB 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-κB, HMGB1, TNF-α and IL-1β 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/22173123/Effects_of_intrathecal_epigallocatechin_gallate_an_inhibitor_of_Toll_like_receptor_4_on_chronic_neuropathic_pain_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(11)01504-4 DB - PRIME DP - Unbound Medicine ER -