The time-course and RNA interference of TNF-α, IL-6, and IL-1β expression on neuropathic pain induced by L5 spinal nerve transection in rats

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

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Neuropathic pain after C7 spinal nerve transection in man

Pain ◽

10.1016/s0304-3959(01)00413-4 ◽

2002 ◽

Vol 96 (1) ◽

pp. 41-47 ◽

Cited By ~ 11

Author(s):

Zahid Ali ◽

Richard A. Meyer ◽

Allan J. Belzberg

Keyword(s):

Neuropathic Pain ◽

Spinal Nerve ◽

Nerve Transection

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Effect of Massage on the TLR4 Signalling Pathway in Rats with Neuropathic Pain

Pain Research and Management ◽

10.1155/2020/8309745 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qian Wang ◽

Jing Lin ◽

Peng Yang ◽

Yingye Liang ◽

Dongming Lu ◽

...

Keyword(s):

Neuropathic Pain ◽

Spinal Nerve ◽

Signalling Pathway ◽

Inflammatory Factors ◽

Control Group ◽

Group Model ◽

Model Group ◽

Expression Levels ◽

Tnf Α ◽

Massage Group

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-α, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-α, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.

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CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain

European Journal of Immunology ◽

10.1002/eji.200737485 ◽

2008 ◽

Vol 38 (2) ◽

pp. 448-458 ◽

Cited By ~ 126

Author(s):

Ling Cao ◽

Joyce A. DeLeo

Keyword(s):

Neuropathic Pain ◽

T Lymphocytes ◽

Spinal Nerve ◽

Nerve Transection

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Role of spinal glial cells in excitability of wide dynamic range neurons and the development of neuropathic pain with the L5 spinal nerve transection in the rats: Behavioral and electrophysiological study

Physiology & Behavior ◽

10.1016/j.physbeh.2019.112597 ◽

2019 ◽

Vol 209 ◽

pp. 112597 ◽

Cited By ~ 1

Author(s):

Laleh Rezaee ◽

Homa Manaheji ◽

Abbas Haghparast

Keyword(s):

Neuropathic Pain ◽

Glial Cells ◽

Dynamic Range ◽

Electrophysiological Study ◽

Spinal Nerve ◽

Nerve Transection ◽

Wide Dynamic Range ◽

Wide Dynamic Range Neurons

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Time course of substance P expression in dorsal root ganglia following complete spinal nerve transection

The Journal of Comparative Neurology ◽

10.1002/cne.20981 ◽

2006 ◽

Vol 497 (1) ◽

pp. 78-87 ◽

Cited By ~ 45

Author(s):

Wendy Weissner ◽

Barbara J. Winterson ◽

Alan Stuart-Tilley ◽

Marshall Devor ◽

Geoffrey M. Bove

Keyword(s):

Substance P ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Time Course ◽

Spinal Nerve ◽

Nerve Transection

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Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization

Molecular Pain ◽

10.1177/1744806921996520 ◽

2021 ◽

Vol 17 ◽

pp. 174480692199652

Author(s):

Feng Zhou ◽

Xian Wang ◽

Baoyu Han ◽

Xiaohui Tang ◽

Ru Liu ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Thermal Hyperalgesia ◽

Short Chain Fatty Acids ◽

Antibiotic Administration ◽

Tnf Α ◽

Microglia Polarization ◽

Inflammatory Phenotype ◽

Phenotype Markers ◽

Anti Inflammatory

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process of microglia polarization towards pro-inflammatory phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active role for the gut microbiota in promoting microglial full maturation and inflammatory capabilities via the production of Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved in pro-inflammatory/anti-inflammatory phenotypes microglia polarization in the neuropathic pain. In the present study, chronic constriction injury (CCI) was used to induce neuropathic pain in mice, the mechanical withdrawal threshold, thermal hyperalgesia were accomplished. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), pro-inflammatory phenotype markers including CD68, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and anti-inflammatory phenotype markers including CD206, IL-4 in the hippocampus and spinal cord were determined on day 21 after CCI. The results showed that CCI produced mechanical allodynia and thermal hyperalgesia, and also increased the expressions of microglia markers (Iba1, CD11b) and pro-inflammatory phenotype markers (CD68, IL-1β, and TNF-α), but not anti-inflammatory phenotype marker (CD206, IL-4) in the hippocampus and spinal cord, accompanied by increased SCFAs in the gut. Notably, antibiotic administration reversed these abnormalities, and its effects was also bloked by SCFAs administration. In conclusion, data from our study suggest that CCI can lead to mechanical and thermal hyperalgesia, while SCFAs play a key role in the pathogenesis of neuropathic pain by regulating microglial activation and subsequent pro-inflammatory phenotype polarization. Antibiotic administration may be a new treatment for neuropathic pain by reducing the production of SCFAs and further inhibiting the process of microglia polarization.

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IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22115657 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5657

Author(s):

Seounghun Lee ◽

Hyo-Jung Shin ◽

Chan Noh ◽

Song-I Kim ◽

Young-Kwon Ko ◽

...

Keyword(s):

Neuropathic Pain ◽

Microglial Activation ◽

Glycolic Acid ◽

Nuclear Factor Kappa B ◽

Decisive Role ◽

Plga Nanoparticles ◽

Spinal Nerve ◽

Nuclear Factor ◽

Interfering Rna

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

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