Novel targets for Spinal Cord Injury related neuropathic pain

Ahmed, Mostafa M.; King, Kevin C; Pearce, Shane M.; Ramsey, Melissa A; Miranpuri, Gurwattan S.; Resnick, Daniel K.

doi:10.5214/ans.0972.7531.1118413

Cited by 18 publications

(15 citation statements)

References 71 publications

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“…Spinal cord injury (Sci) results from neurological damage in the spinal cord and leads to serious impairment of sensorimotor functions, along with other side effects (1), such as paraplegia and tetraplegia (2,3). Patients with Sci suffer from pain (4). There has been substantial research exploring pathophysiological changes that occur post-Sci (5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Chen

Qin

2020

Mol Med Report

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Micrornas (mirs) play an important role in the development and progression of spinal cord injury (Sci). The role of mir-138-5p in Sci was investigated in the present study. The anti-inflammatory effects of miR-138-5p and underlying mechanisms were investigated in an Sci rat model and in vitro model. reverse transcription-quantitative Pcr (rT-qPcr) was used to examine the expression of mir-138-5p in the Sci in vivo and in vitro models, as well as patients with Sci; it was found that miR-138-5p was significantly upregulated in Sci. Bioinformatics and dual-luciferase reporter assays were performed to predict and confirm the binding sites between mir-138-5p and the 3'untranslated region of sirtuin 1 (SirT1). Then, the expression of SirT1 was detected via rT-qPcr and western blotting, indicating downregulation of SIRT1 in SCI. PC12 cells were transfected with miR-138-5p inhibitor, inhibitor control or miR-138-5p inhibitor + SIRT1 small interfering RNA for 48 h, and then subjected to lipopolysaccharide (100 ng/ml) treatment for 4 h. Then, MTT assay, flow cytometry and eliSa experiments were performed to analyze cell viability, apoptosis, and the levels of tumor necrosis factor-α, interleukin (il)-1β and il-6. Findings suggested that downregulation of miR-138-5p increased PC12 cell viability, inhibited cell apoptosis and attenuated proinflammatory responses, which may result in amelioration of Sci. However, all these effects were reversed by SIRT1 knockdown. Finally, it was observed that miR-138-5p altered the related protein expression of the PTen/aKT pathway. These results indicated that miR-138-5p could regulate inflammatory responses and cell apoptosis in SCI models by modulating the PTEN/AKT signaling pathway via SirT1, thus playing an important role in the development of Sci. collectively, the present study demonstrated that miR-138-5p may be a novel therapeutic target for the treatment of Sci. Materials and methodsClinical samples. a total of 18 serum specimens from patients with Sci (age range, 27-58 years; 12 male patients and 6 female MicroRNA-138-5p regulates the development of spinal cord injury by targeting SIRT1 JincHuan cHen and ruJie Qin department of Spine Surgery, The First People's Hospital of lianyungang, lianyungang, Jiangsu 222000, P.r. china

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Chen

Qin

2020

Mol Med Report

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“…Patients with spinal cord injury (SCI) suffer from extreme pain while exercising (1). This results in a notable decrease in quality of life, and a heavy burden on family members and society (2).…”

Section: Introductionmentioning

confidence: 99%

“…However, improving neurological functional repair after damage still remains a challenge. Local inflammatory response is a major factor that influences damage repair (1). The inflammatory response is regarded as a double-edged sword.…”

Section: Introductionmentioning

confidence: 99%

miRNA‑146a attenuates inflammation in an in�vitro spinal cord injury model via inhibition of TLR4 signaling

Tan

Zhang

et al. 2018

Exp Ther Med

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The present study evaluated the anti-inflammatory effect of microRNA (miR)-146a in a spinal cord injury (SCI) rat model and model, and explored possible underlying mechanisms of this effect. miR-146a expression was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 content was measured using ELISA kits. Inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88) and phosphorylated (p)-nuclear factor (NF)-κB were measured using western blotting. In the SCI rat model, miR-146a expression was downregulated. In the model, downregulation of miR-146a increased inflammation, enhanced iNOS and PGE2 protein expression and induced TLR4, MyD88 and NF-κB expression. Overexpression of miR-146a reduced inflammation, iNOS and PGE2 protein expression, and suppressed TLR4, MyD88 and NF-κB expression in the SCI model. The inhibition of TLR4 attenuated the proinflammatory effects of anti-miR-146a in the SCI model. The results indicate that miR-146a reduces inflammation in an SCI model through the TLR4-NF-κB signaling pathway. The present study demonstrated that miR-146a may be a promising therapeutic agent for SCI.

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“…MMPs are able to interact with numerous cell surfaces and soluble proteins including growth factors, adhesion molecules, receptors, cytokines, and chemokines [9] . MMP-9 and MMP-2 are 2 groups of MMPs that play a significant role in secondary physiological recovery following a SCI [10] . MMP-9 and MMP-2 are known to be overexpressed in the acute and chronic phases of NP post SCI [10] .…”

Section: Introductionmentioning

confidence: 99%

“…MMP-9 and MMP-2 are 2 groups of MMPs that play a significant role in secondary physiological recovery following a SCI [10] . MMP-9 and MMP-2 are known to be overexpressed in the acute and chronic phases of NP post SCI [10] . We have demonstrated the up-regulation of MMP-2 in animals in pain (thermal hyperalgesia, TH+) and no pain (TH-) following 21 through 42 days of contusion SCI ( fig.…”

Section: Introductionmentioning

confidence: 99%

Implication of Hypothalamus in Alleviating Spinal Cord Injury-Induced Neuropathic Pain

et al. 2016

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Neuropathic pain (NP) is common among spinal cord injury (SCI) patients, and there remain clinical difficulties in treating NP due to the lack of understanding of underlying mechanisms. Extracellular proteins, such as matrix metalloproteinase and β-catenin, have been shown to be activated in the spinal cord regions following an injury, and may play a key role in contributing to NP states. While these extracellular proteins have been used as therapeutic targets in the spinal cord, there has also been evidence of up-regulation in the hypothalamus following a SCI. We hypothesize that the hypothalamus is involved in regulating NP following a SCI, and hence should be researched further to determine if it is a viable target for future therapeutic treatments.

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Novel targets for Spinal Cord Injury related neuropathic pain

Cited by 18 publications

References 71 publications

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

miRNA‑146a attenuates inflammation in an in�vitro spinal cord injury model via inhibition of TLR4 signaling

Implication of Hypothalamus in Alleviating Spinal Cord Injury-Induced Neuropathic Pain

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