scholarly journals Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qun Wang ◽  
Yanyuan Sun ◽  
Yingna Ren ◽  
Yandong Gao ◽  
Li Tian ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Messenger Rna ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Cellular Localization ◽  
Altered Expression

Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

scholarly journals Thiamine Suppresses Thermal Hyperalgesia, Inhibits Hyperexcitability, and Lessens Alterations of Sodium Currents in Injured, Dorsal Root Ganglion Neurons in Rats

2009 ◽  
Vol 110 (2) ◽  
pp. 387-400 ◽  
Author(s):  
Xue-Song Song ◽  
Zhi-Jiang Huang ◽  
Xue-Jun Song
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Thermal Hyperalgesia ◽  
B Vitamins ◽  
Drg Neurons ◽  
Na Currents

Background B vitamins can effectively attenuate inflammatory and neuropathic pain in experimental animals, while their efficacy in treating clinical pain syndromes remains unclear. To understand possible mechanisms underlying B vitamin-induced analgesia and provide further evidence that may support the clinical utility of B vitamins in chronic pain treatment, this study investigated effects of thiamine (B1) on the excitability and Na currents of dorsal root ganglion (DRG) neurons that have been altered by nerve injury. Methods Nerve injury was mimicked by chronic compression of DRG in rats. Neuropathic pain was evidenced by the presence of thermal hyperalgesia. Intracellular and patch-clamp recordings were made in vitro from intact and dissociated DRG neurons, respectively. Results (1) In vivo intraperitoneal administration of B1 (66 mg/kg/day, 10-14 doses) significantly inhibited DRG compression-induced neural hyperexcitability, in addition to suppressing thermal hyperalgesia. (2) In vitro perfusion of B1 (0.1, 1 and 10 mM) resulted in a dose-dependent inhibition of DRG neuron hyperexcitability. In addition, the DRG neurons exhibited size-dependent sensitivity to B1 treatment, i.e., the small and the medium-sized neurons, compared to the large neurons, were significantly more sensitive. (3) Both in vitro (1 mM) and in vivo application of B1 significantly reversed DRG compression-induced down-regulation of tetrodotoxin-resistant but not tetrodotoxin-sensitive Na current density in the small neurons. B1 at 1 mM also reversed the compression-induced hyperpolarizing shift of the inactivation curve of the tetrodotoxin-resistant currents and the upregulated ramp currents in small DRG neurons. Conclusion Thiamine can reduce hyperexcitability and lessen alterations of Na currents in injured DRG neurons, in addition to suppressing thermal hyperalgesia.

scholarly journals Microglial BDNF, PI3K, and p-ERK in the Spinal Cord Are Suppressed by Pulsed Radiofrequency on Dorsal Root Ganglion to Ease SNI-Induced Neuropathic Pain in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Xueru Xu ◽  
Shaoxiong Fu ◽  
Xiaomei Shi ◽  
Rongguo Liu
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Calcium Binding ◽  
Dorsal Root ◽  
Intrathecal Injection ◽  
Pulsed Radiofrequency ◽  
Erk Phosphorylation ◽  
Extracellular Signal

Background. Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) has been applied to alleviate neuropathic pain effectively, yet the mechanisms underlying pain reduction owing to this treatment are not clarified completely. The activated microglia, brain-derived neurotrophic factor (BDNF), phosphatidylinositol 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal cord were demonstrated to be involved in developing neuropathic pain. Also, it has been just known that PRF on DRG inhibits the microglial activation in nerve injury rats. Here, we aim to investigate whether PRF treatment could regulate the levels of BDNF, PI3K, and p-ERK in the spinal cord of rats with spared nerve injury (SNI) via suppressing the spinal microglia activation to ease neuropathic pain. Methods. The rats with SNI were intrathecally treated with minocycline (specific microglia inhibitor) or same volume of dimethyl sulfoxide once daily, beginning from 1 h before nerve transection to 7 days. PRF was applied adjacent to the L4-L5 DRG of rats with SNI at 45 V for 6 min on the seventh postoperative day, whereas the free-PRF rats were treated without PRF. The withdrawal thresholds were studied, and the spinal levels of ionized calcium-binding adapter molecule 1 (Iba1), BDNF, PI3K, and p-ERK were calculated by western blot analysis, reverse transcription-polymerase chain reaction, and immunofluorescence. Results. The paw withdrawal mechanical threshold and paw withdrawal thermal latency decreased in the ipsilateral hind paws after SNI, and the spinal levels of Iba1, BDNF, PI3K, and p-ERK increased on day 21 after SNI compared with baseline (P<0.01). An intrathecal injection of minocycline led to the reversal of SNI-induced allodynia and increase in levels of Iba1, BDNF, PI3K, and p-ERK. Withdrawal thresholds recovered partially after a single PRF treatment for 14 days, and SNI-induced microglia hyperactivity, BDNF upregulation, and PI3K and ERK phosphorylation in the spinal cord reduced on D14 due to the PRF procedure. Conclusion. Microglial BDNF, PI3K, and p-ERK in the spinal cord are suppressed by the therapy of PRF on DRG to ease SNI-induced neuropathic pain in rats.

Anion exchanger 3 in dorsal root ganglion contributes to nerve injury-induced chronic mechanical allodynia and thermal hyperalgesia

2018 ◽  
Vol 70 (3) ◽  
pp. 374-382 ◽  
Author(s):  
Marian J. Pérez-Rodríguez ◽  
Isabel Velazquez-Lagunas ◽  
Alejandro Pluma-Pluma ◽  
Paulino Barragán-Iglesias ◽  
Vinicio Granados-Soto
Keyword(s):  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Anion Exchanger ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia

Contralateral Neuropathic Pain and Neuropathology in Dorsal Root Ganglion and Spinal Cord Following Hemilateral Nerve Injury in Rats

Spine ◽  
2008 ◽  
Vol 33 (12) ◽  
pp. 1344-1351 ◽  
Author(s):  
Satoshi Hatashita ◽  
Miho Sekiguchi ◽  
Hideo Kobayashi ◽  
Shin-ichi Konno ◽  
Shin-ichi Kikuchi
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root

scholarly journals The Delayed-Onset Mechanical Pain Behavior Induced by Infant Peripheral Nerve Injury Is Accompanied by Sympathetic Sprouting in the Dorsal Root Ganglion

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Pei Liu ◽  
Qing Zhang ◽  
You-shui Gao ◽  
Yi-Gang Huang ◽  
Junjie Gao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Nerve Lesion ◽  
Adult Rats ◽  
Delayed Onset ◽  
Sympathetic Sprouting ◽  
Heat Hyperalgesia ◽  
Time Point

Background. Sympathetic sprouting in the dorsal root ganglion (DRG) following nerve injuries had been proved to induce adult neuropathic pain. However, it is unclear whether the abnormal sprouting occurs in infant nerve injury. Methods. L5 spinal nerve ligation (SNL) or sham surgery was performed on adult rats and 10-day-old pups, and mechanical thresholds and heat hyperalgesia were analyzed on 3, 7, 14, 28, and 56 postoperative days. Tyrosine hydroxylase-labeled sympathetic fibers were observed at each time point, and 2 neurotrophin receptors (p75NTR and TrkA) were identified to explore the mechanisms of sympathetic sprouting. Results. Adult rats rapidly developed mechanical and heat hyperalgesia from postoperative day 3, with concurrent sympathetic sprouting in DRG. In contrast, the pup rats did not show a significantly lower mechanical threshold until postoperative day 28, at which time the sympathetic sprouting became evident in the DRG. No heat hyperalgesia was presented in pup rats at any time point. There was a late expression of glial p75NTR in DRG of pups from postoperative day 28, which was parallel to the occurrence of sympathetic sprouting. The expression of TrkA did not show such a postoperative syncing change. Conclusion. The delayed-onset mechanical allodynia in the infant nerve lesion was accompanied with parallel sympathetic sprouting in DRG. The late parallel expression of glial p75NTR injury may play an essential role in this process, which provides novel insight into the treatment of delayed adolescent neuropathic pain.

Receptor Subtype Mediating the Adrenergic Sensitivity of Pain Behavior and Ectopic Discharges in Neuropathic Lewis Rats

1999 ◽  
Vol 81 (5) ◽  
pp. 2226-2233 ◽  
Author(s):  
Doo Hyun Lee ◽  
Xianzeng Liu ◽  
Hyun Taek Kim ◽  
Kyungsoon Chung ◽  
Jin Mo Chung
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Pain Behavior ◽  
Receptor Subtype ◽  
Systemic Injection ◽  
Lewis Rats ◽  
Ectopic Discharges

Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of α-adrenergic receptor (α-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general α-AR blocker. We examined the effects of specific α1- and α2-AR blockers on 1) behavioral signs of mechanical allodynia, 2) ectopic discharges recorded in the in vivo condition, and 3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed α1- and α2-AR antagonist) or terazosin (TRZ, an α1-AR antagonist) but not by various α2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the α1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving α1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the α1 subtype of AR.

scholarly journals Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yu-Juan Qu ◽  
Xiao Zhang ◽  
Zhen-Zhen Fan ◽  
Juan Huai ◽  
Yong-Bo Teng ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Mapk Pathway ◽  
Intrathecal Injection ◽  
Ruthenium Red ◽  
Protein Expressions ◽  
Intermediary Role ◽  
Ectopic Discharges

The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

scholarly journals Pulsed Radiofrequency on Dorsal Root Ganglion Improves Neuropathic Pain-induced Depression in SNI Rats by Regulating Hippocampal BDNF and Neuroinflammation via Spinal IRF8 Inactivation

2021 ◽  
Author(s):  
Xueru Xu ◽  
Zhisen Dai ◽  
Chun Lin ◽  
Fan Lin ◽  
Rongguo Liu
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Intrathecal Injection ◽  
Free Water ◽  
Sucrose Preference ◽  
Pulsed Radiofrequency ◽  
Tnf Α ◽  
Immobility Time

Abstract Background: Increasing evidence suggests that neuroglia, neuroimmune, and neuroinflammatory processes are involved in the development of nerve injury-induced pain and depression. Interferon regulatory factor 8 (IRF8), a crucial factor for microglial activation, is essential for the development of neuropathic pain. The brain-derived neurotrophic factor (BDNF) and inflammatory mediators (IL-1β, IL-6, and TNF-α) in the hippocampus contribute to the pathophysiology of neuropathic pain-depression comorbidity. Our previous study found that depressive-like behaviors induced by spared nerve injury (SNI) could be improved by applying pulsed radiofrequency (PRF) to the dorsal root ganglion (DRG) (PRF-DRG). However, the anti-depressive mechanisms of PRF-DRG therapy remain largely unknown. Methods: All rats (except for those in the sham group) were subjected to SNI. The nuclease-free water group and the IRF8 siRNA group were intrathecally injected with nuclease-free water and IRF8 siRNA on days 5 and 6 after SNI, respectively. PRF therapy on the L5 DRG was performed in the PRF group on day 7 after SNI, whereas no PRF current was delivered in the Sham-PRF group. The 50% paw withdrawal threshold, forced swimming test, and sucrose preference test were performed. The expression levels of spinal IRF8 and hippocampal BDNF were tested by molecular biochemistry, while IL-1β, IL-6, and TNF-α were tested by ELISA.Results: The depressive-like behaviors induced by SNI were remarkably developed in rats, which was indicated by a significant reduction in the sucrose preference rate and prolonged immobility time on day 42 after SNI. Mechanical allodynia and depression-like behaviors of rats with SNI were remarkably improved after PRF-DRG or intrathecal IRF8 siRNA. Spinal IRF8 overexpression, hippocampal BDNF downregulation, and increased hippocampal IL-1β and TNF-α levels were reversed by PRF-DRG, similar to the intrathecal injection of IRF8 siRNA. Conclusions: PRF-DRG therapy could regulate neuroimmune and neuroinflammatory responses to improve pain-induced depressive-like behaviors. The beneficial effect was correlated with the upregulation of BDNF and inhibition of IL-1β and TNF-α in the hippocampus via spinal IRF8 inactivation.

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