scholarly journals Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenyu Wu ◽  
Xiaofang Lu ◽  
Shengsheng Zhang ◽  
Chunyang Zhu
Keyword(s):  
Gene Expression ◽  
Dorsal Horn ◽  
Functional Dyspepsia ◽  
Rat Model ◽  
Spinal Dorsal Horn ◽  
Visceral Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gastric Distention ◽  
Real Time Quantitative Pcr ◽  
Spinal Dorsal

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

scholarly journals TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

2016 ◽  
Vol Volume 9 ◽  
pp. 1153-1160 ◽  
Author(s):  
Qian Li ◽  
Chenghao Guo ◽  
Mohammed Ali Chowdhury ◽  
Taoli Dai ◽  
Wei Han
Keyword(s):  
Dorsal Horn ◽  
Rat Model ◽  
Spinal Dorsal Horn ◽  
Visceral Hypersensitivity ◽  
In Vivo Study ◽  
Spinal Dorsal

Intrathecal injection of GDNF and BDNF induces immediate early gene expression in rat spinal dorsal horn

2005 ◽  
Vol 194 (1) ◽  
pp. 255-266 ◽  
Author(s):  
J.L.M. Jongen ◽  
E.D. Haasdijk ◽  
H. Sabel-Goedknegt ◽  
J. van der Burg ◽  
Ch.J. Vecht ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Intrathecal Injection ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Spinal Dorsal

scholarly journals Resveratrol Mediates Mechanical Allodynia Through Modulating Inflammatory Response via the TREM2-autophagy Axis in SNI Rat Model

2020 ◽  
Author(s):  
Yaping Wang ◽  
Yu Shi ◽  
Yongquan Huang ◽  
Wei Liu ◽  
Guiyuan Cai ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Response ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Spinal Dorsal Horn ◽  
Intrathecal Administration ◽  
Spared Nerve Injury ◽  
Spinal Dorsal

Abstract Background Neuropathic pain (NeuP) is a chronic and challenging clinical problem, with little effective treatment. Resveratrol has shown neuroprotection by inhibiting inflammatory response in NeuP. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2) expressed by microglia was identified as a critical factor of inflammation in nervous system diseases. In this study, we explored whether resveratrol could ameliorate neuroinflammation and produce anti-mechanical allodynia effects via regulating TREM2 in spared nerve injury rats, as well as investigated the underlying mechanisms. Methods A spared nerve injury (SNI) rat model was performed to investigate whether resveratrol could exert anti-mechanism allodynia effects via inhibiting neuroinflammation. To evaluate the role of TREM2 in anti-neuroinflammatory function of resveratrol, Lentivirus coding TREM2 was intrathecal injected into SNI rats to activate TREM2 and the pain behavior was detected by the Von Frey test. Furthermore, 3-Methyladenine (3-MA, an autophagy inhibitor) was performed to analyze the molecular mechanisms of resveratrol-mediated anti-neuroinflammation using Western blot, qPCR, immunofluorescence. Results The TREM2 expression and number of the microglial cell was significantly increased in the ipsilateral spinal dorsal horn after SNI. We found that intrathecal administration of resveratrol (300ug/day) alleviated mechanical allodynia; obviously enhanced autophagy; and markedly reduced the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ipsilateral spinal dorsal horn after SNI. Moreover, the number of Iba-1+ microglial cells and TREM2 expression were downregulated after resveratrol treatment. Intrathecal administration of lentivirus coding TREM2 and/or 3-methyladenine in those rats induced deficiencies in resveratrol-mediated anti-inflammation, leading to mechanical allodynia that could be rescued via administration of Res. Furthermore, 3-MA treatment contributed to TREM2-mediated mechanical allodynia. Conclusions Taken together, these data reveal that resveratrol relieves neuropathic pain through suppressing microglia-mediated neuroinflammation via regulating the TREM2-autophagy axis in SNI rats.

scholarly journals Targeting spinal TRAF6 expression attenuates chronic visceral pain in adult rats with neonatal colonic inflammation

2020 ◽  
Vol 16 ◽  
pp. 174480692091805 ◽  
Author(s):  
Rui-Xia Weng ◽  
Wei Chen ◽  
Jia-Ni Tang ◽  
Qian Sun ◽  
Meng Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Colonic Inflammation ◽  
Spinal Dorsal ◽  
Irritable Bowel

Background Irritable bowel syndrome is one of the most common gastrointestinal disorders. It is featured by abdominal pain in conjunction with altered bowel habits. However, the pathophysiology of the syndrome remains largely unknown. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be involved in neuropathic pain. The aim of this study was to investigate roles and mechanisms of TRAF6 in the chronic visceral hypersensitivity. Methods Visceral hypersensitivity was induced by neonatal colonic inflammation and was identified by colorectal distention. The protein level, RNA level, and cellular distribution of TRAF6 and its related molecules were detected with Western blot, quantitative polymerase chain reaction, and immunofluorescence. In vitro spinal cord slice recording technique was performed to determine the synaptic transmission activities. Results Neonatal colonic inflammation rats displayed visceral hypersensitivity at the age of six weeks. The expression of TRAF6 was obviously upregulated in spinal cord dorsal horn of neonatal colonic inflammation rats at the age of six weeks. Immunofluorescence study showed that TRAF6 was dominantly expressed in spinal astrocytes. Intrathecal injection of TRAF6 small interfering RNA (siRNA) significantly reduced the amplitude of spontaneous excitatory postsynaptic currents at the spinal dorsal horn level. Furthermore, knockdown of TRAF6 led to a significant downregulation of cystathionine β synthetase expression in the spinal dorsal horn of neonatal colonic inflammation rats. Importantly, intrathecal injection of TRAF6 siRNA remarkably alleviated visceral hypersensitivity of neonatal colonic inflammation rats. Conclusions Our results suggested that the upregulation of TRAF6 contributed to visceral pain hypersensitivity, which is likely mediated by regulating cystathionine β synthetase expression in the spinal dorsal horn. Our findings suggest that TRAF6 might act as a potential target for the treatment of chronic visceral pain in irritable bowel syndrome patients.

Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

2013 ◽  
Vol 19 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Hee Kyung Cho ◽  
Yun Woo Cho ◽  
Eun Hyuk Kim ◽  
Menno E. Sluijter ◽  
Se Jin Hwang ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Lumbar Disc Herniation ◽  
Disc Herniation ◽  
Rat Model ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Lumbar Disc ◽  
Exposed Group ◽  
Pulsed Radiofrequency ◽  
Spinal Dorsal

Object Herniated discs can induce sciatica by mechanical compression and/or chemical irritation caused by proinflammatory cytokines. Using immunohistochemistry methods in the dorsal horn of a rat model of lumbar disc herniation, the authors investigated the effects of pulsed radiofrequency (PRF) current administration to the dorsal root ganglion (DRG) on pain-related behavior and activation of microglia, astrocytes, and mitogen-activated protein kinase. Methods A total of 33 Sprague-Dawley rats were randomly assigned to either a sham-operated group (n = 10) or a nucleus pulposus (NP)–exposed group (n = 23). Rats in the NP-exposed group were further subdivided into NP exposed with sham stimulation (NP+sham stimulation, n = 10), NP exposed with PRF (NP+PRF, n = 10), or euthanasia 10 days after NP exposure (n = 3). The DRGs in the NP+PRF rats were exposed to PRF waves (2 Hz) for 120 seconds at 45 V on postoperative Day 10. Rats were tested for mechanical allodynia 10 days after surgery and at 8 hours, 1 day, 3 days, 10 days, 20 days, and 40 days after PRF administration. Immunohistochemical staining of astrocytes (glial fibrillary acidic protein), microglia (OX-42), and phosphorylated extracellular signal–regulated kinases (pERKs) in the spinal dorsal horn was performed at 41 days after PRF administration. Results Starting at 8 hours after PRF administration, mechanical withdrawal thresholds dramatically increased; this response persisted for 40 days (p < 0.05). After PRF administration, immunohistochemical expressions of OX-42 and pERK in the spinal dorsal horn were quantitatively reduced (p < 0.05). Conclusions Pulsed radiofrequency administration to the DRG reduced mechanical allodynia and downregulated microglia activity and pERK expression in the spinal dorsal horn of a rat model of lumbar disc herniation.

Spinal Dorsal Horn Gene Expression Following Loose Ligation of the Rat Sciatic Nerve

2007 ◽  
Vol 14 (2) ◽  
pp. 24-29
Author(s):  
Daniel K Resnick ◽  
Raghu Vemuganti ◽  
Gurwattan S Miranpuri ◽  
Gordana Miletic ◽  
Vjekoslav Miletic
Keyword(s):  
Gene Expression ◽  
Sciatic Nerve ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spinal Dorsal ◽  
Rat Sciatic Nerve
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