Changes in Expression of mRNA for Interleukin-8 and Effects of Interleukin-8 Receptor Inhibitor in the Spinal Dorsal Horn in a Rat Model of Lumbar Disc Herniation

Spine ◽  
2011 ◽  
Vol 36 (25) ◽  
pp. 2139-2146 ◽  
Author(s):  
Su-Jeong Kim ◽  
Sung-Min Park ◽  
Yun-Woo Cho ◽  
Yong-Jae Jung ◽  
Dong-Gyu Lee ◽  
...  
2013 ◽  
Vol 19 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Hee Kyung Cho ◽  
Yun Woo Cho ◽  
Eun Hyuk Kim ◽  
Menno E. Sluijter ◽  
Se Jin Hwang ◽  
...  

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.


2016 ◽  
Vol 8;19 (8;11) ◽  
pp. E1197-E1209
Author(s):  
Sang Ho Ahn

Background: Herniated lumbar discs can induce sciatica by mechanical compression and/ or chemical irritation. It was recently reported that neuroglial cellular activity after pulsed radiofrequency (PRF) application to a single dorsal root ganglion (DRG) attenuated neuroglial activity at the corresponding spinal dorsal horn. Recently, caudal epidural PRF has been used to manage neuropathic pain, but evidence of molecular changes after the administration of caudal epidural PRF to attenuate neuropathic pain is lacking, and it has not been determined whether caudal epidural PRF affects neuroglial activity at different spinal levels. Objectives: Using immunohistochemical methods in a rat model of lumbar disc herniation, the authors investigated the effects of caudal epidural PRF administration on pain-related behavior, on the activations of microglia and astrocytes in spinal cord, and on the expressions of calcitonin gene-related peptide (CGRP) and Transient receptor potential vanilloid 1(TRPV1) in the DRG at the L3, L4, L5, L6, and S1 levels. Study Design: Controlled animal trial. Setting: University hospital laboratory. Methods: Forty-five Sprague-Dawley rats were randomly assigned to a sham-operated group (n = 10) or a nucleus pulposus (NP)-exposed group (n = 35). Rats in the NP-exposed group were further subdivided into a NP-exposed with sham stimulation group (the NP-nonPRF group; n = 13) or a NP exposed with caudal epidural PRF stimulation group (the NP-PRF group; n = 22). Pulsed radiofrequency was administered on postoperative day 10 (POD 10) by placing an electrode in the caudal epidural space through the sacral hiatus and administering 5 Hz of PRF current for 600 seconds (maximum tip temperature 42°C). Rats were tested for mechanical allodynia on POD 10 and on days 7 and 14 after caudal epidural PRF administration (post-PRF). At 14 days post-PRF, sections of the spinal cord from L3, L4, L5, L6, and S1 were immunostained for ionized calciumbinding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), and DRGs from the same levels were immunostained for CGRP and TRPV1. Results: Mechanical withdrawal thresholds increased at 7 days post-PRF (P = 0.04), and the immunohistochemical expression of Iba1 in the L5 spinal dorsal horn and of CGRP in the L5 DRG were quantitatively reduced (P < 0.001) at 14 days post-PRF. Furthermore, the upregulations of Iba1 at L3, L4, L6, and S1 dorsal horns and CGRP at L6 DRG were also attenuated by caudal epidural PRF (P < 0.001). Limitation: We examined molecular changes only in ipsilateral lumbar regions and at 14 days post-PRF. Conclusion: Caudal epidural PRF reduced mechanical allodynia and downregulated microglia activity and CGRP expression at the lumbar disc herniated level and in adjacent lumbar spinal levels in a rat model of lumbar disc herniation. Key words: Caudal, pulsed radiofrequency, multisegmental, lumbar disc herniation, microglia, calcitonin gene-related peptide


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenyu Wu ◽  
Xiaofang Lu ◽  
Shengsheng Zhang ◽  
Chunyang Zhu

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.


Spine ◽  
2005 ◽  
Vol 30 (2) ◽  
pp. 188-193 ◽  
Author(s):  
Akira Onda ◽  
Yasuaki Murata ◽  
Björn Rydevik ◽  
Karin Larsson ◽  
Shinichi Kikuchi ◽  
...  

2003 ◽  
Vol 3 (5) ◽  
pp. 82
Author(s):  
Masahiro Kanayama ◽  
Tomoyuki Hashimoto ◽  
Keiichi Shigenobu ◽  
Shigeru Yamane

2020 ◽  
Author(s):  
Yaping Wang ◽  
Yu Shi ◽  
Yongquan Huang ◽  
Wei Liu ◽  
Guiyuan Cai ◽  
...  

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.


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