Changes of Toll-like receptor 4 and its downstream cytokines in spinal cord of rat model of neuropathic pain

Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague-Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment; (2) sham burn with HBO treatment; (3) burn with one-week sham HBO treatment; (4) burn with two-week sham HBO treatment; (5) burn with one-week HBO treatment; and (6) burn with two-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting. A behavior test was also conducted, which revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared to the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor α (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis showed that the expression of Gal-3, TLR-4, CD68 and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia and macrophage activation in a rat model.

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Activation of GABAB Receptor Suppresses Diabetic Neuropathic Pain through Toll-Like Receptor 4 Signaling Pathway in the Spinal Dorsal Horn

Mediators of Inflammation ◽

10.1155/2018/6016272 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Peng Liu ◽

Hong-Bin Yuan ◽

Shuang Zhao ◽

Fei-Fei Liu ◽

Yu-Qing Jiang ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Signaling Pathway ◽

Gabab Receptor ◽

Intrathecal Injection ◽

Spinal Cord Tissue ◽

Gamma Aminobutyric Acid ◽

Toll Like Receptor ◽

Diabetic Neuropathic Pain ◽

Toll Like Receptor 4

Diabetic neuropathic pain (DNP) is a prevalent complication in diabetes patients. Neuronal inflammation and activation of Toll-like receptor 4 (TLR4) are involved in the occurrence of DNP. However, the underlying mechanisms remain unclear. Downregulation of gamma-aminobutyric acid B (GABAB) receptor contributes to the DNP. GABAB receptor interacts with NF-κB, a downstream signaling factor of TLR4, in a neuropathic pain induced by chemotherapy. In this study, we determined the role of TLR4/Myd88/NF-κB signaling pathways coupled to GABAB receptors in the generation of DNP. Intrathecal injection of baclofen (GABAB receptor agonist), LPS-RS ultrapure (TLR4 antagonist), MIP (MyD88 antagonist), or SN50 (NF-κB inhibitor) significantly increased paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) in DNP rats, while intrathecal injection of saclofen (GABAB receptor blocker) decreased PWT and PWTL in DNP rats. The expression of TLR4, Myd88, NF-κBp65, and their downstream components IL-1 and TNF-α was significantly higher in the spinal cord tissue in DNP rats compared to control rats. Following inhibition of TLR4, Myd88, and NF-κB, the expression of IL-1 and TNF-α decreased. Activation of GABAB receptors downregulated the expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. Blockade of GABAB receptors significantly upregulated expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. These data suggest that activation of the TLR4/Myd88/NF-κB signaling pathway is involved in the occurrence of DNP in rats. Activation of GABAB receptor in the spinal cord may suppress the TLR4/Myd88/NF-κB signaling pathway and alleviate the DNP.

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Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain

International Journal of Medical Sciences ◽

10.7150/ijms.7.251 ◽

2010 ◽

pp. 251-259 ◽

Cited By ~ 43

Author(s):

Fei-xiang Wu ◽

Jin-jun Bian ◽

Xue-rong Miao ◽

Sheng-dong Huang ◽

Xue-wu Xu ◽

...

Keyword(s):

Neuropathic Pain ◽

Rat Model ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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BOLD FMRI OF BRAIN ACTIVATION IN RESPONSE TO DIFFERENT SPINAL CORD STIMULATION PARADIGMS IN A RAT MODEL OF CHRONIC NEUROPATHIC PAIN

10.26226/morressier.5ab3c881a874c60026559420 ◽

2018 ◽

Author(s):

Koen Meuwissen

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Rat Model ◽

Spinal Cord Stimulation ◽

Brain Activation ◽

Chronic Neuropathic Pain ◽

Bold Fmri

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(+)-Naloxone, an Opioid-Inactive Toll-Like Receptor 4 Signaling Inhibitor, Reverses Multiple Models of Chronic Neuropathic Pain in Rats

Journal of Pain ◽

10.1016/j.jpain.2012.02.005 ◽

2012 ◽

Vol 13 (5) ◽

pp. 498-506 ◽

Cited By ~ 60

Author(s):

Susannah S. Lewis ◽

Lisa C. Loram ◽

Mark R. Hutchinson ◽

Chien-Ming Li ◽

Yingning Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Multiple Models ◽

Toll Like Receptor ◽

Chronic Neuropathic Pain ◽

Toll Like Receptor 4

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Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway in a Rat Model

10.20944/preprints201807.0136.v1 ◽

2018 ◽

Author(s):

Zong-Sheng Wu ◽

Jing-Jou Lo ◽

Sheng-Hua Wu ◽

Chau-Zen Wang ◽

Rong-Fu Chen ◽

...

Keyword(s):

Spinal Cord ◽

Treatment Group ◽

Dorsal Horn ◽

Burn Injury ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Sd Rats ◽

Galectin 3 ◽

The Right ◽

Behavior Test

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

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