Inhibition of sympathetic sprouting in <scp>CCD</scp> rats by lacosamide

Wang, Y.; Huo, Fu-Quan

doi:10.1002/ejp.1246

Cited by 7 publications

(10 citation statements)

References 41 publications

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“…In other pain models we and others have observed that, as in this study, any manipulation that reduces abnormal spontaneous activity of sensory neurons improves pain behaviors (Devor M, 2009;Xie W, Strong JA, Kim D, Shahrestani S and Zhang JM, 2012;Xie W et al, 2009;Xie W, Strong JA and Zhang JM, 2015;Xie W, Tan ZY, Barbosa C, Strong JA, Cummins TR and Zhang J-M, 2016). In the CCD model, drugs that blocked spontaneous activity or targeted sodium channels while improving pain behaviors include thiamine, (Song XS, Huang ZJ and Song XJ, 2009) local bupivacaine nanoparticles, (Wang T et al, 2018) and lacosamide (Wang Y and Huo F, 2018). The spontaneous activity we observed was predominantly in cells with action potential durations <1.5 msec; these were likely predominantly cells with myelinated axons based on a subset of cells with measured conduction velocities.…”

Section: Discussionsupporting

confidence: 57%

“…Both CCD and LID models induce sympathetic sprouting in the DRG (Chien SQ et al, 2005;Xie WR, Deng H, Li H, Bowen TL, Strong JA and Zhang J-M, 2006). After CCD, sensory neurons may develop increased sensitivity to adrenergic and other sympathetic transmitters such as neuropeptide Y; conversely, blocking Na channels may have improved pain in part by reducing sympathetic sprouting (Wang Y and Huo F, 2018;Xie W et al, 2011;Zhang J-M et al, 2004). However, it is difficult to attribute all the behavioral effects of Na channel knockdown in our study to reduction of sympathetic sprouting into the DRG, as the behavioral effects were marked even on POD 1 while sympathetic sprouting develops more slowly (Chien SQ, Li C, Li H, Xie W, Pablo CS and Zhang JM, 2005).…”

Section: Discussionmentioning

confidence: 99%

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Role of NaV1.6 and NaVβ4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia

et al. 2019

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Low back pain is a common cause of chronic pain and disability. It is modeled in rodents by chronically compressing the lumbar dorsal root ganglia (DRG) with small metal rods, resulting in ipsilateral mechanical and cold hypersensitivity, and hyperexcitability of sensory neurons. Sodium channels are implicated in this hyperexcitability, but the responsible isoforms are unknown. In this study, we used siRNA-mediated knockdown of the pore-forming Na V 1.6 and regulatory Na V β4 sodium channel isoforms that have been previously implicated in a different model of low back pain caused by locally inflaming the L5 DRG. Knockdown of either subunit markedly reduced spontaneous pain and mechanical and cold hypersensitivity induced by DRG compression, and reduced spontaneous activity and hyperexcitability of sensory neurons with action potentials <1.5 msec (predominately cells with myelinated axons, based on conduction velocities measured in a subset of cells) 4 days after DRG compression. These results were similar to those previously obtained in the DRG inflammation model and some neuropathic pain models, in which sensory neurons other than nociceptors seem to play key roles. The cytokine profiles induced by DRG compression and DRG inflammation were also very similar, with upregulation of several type 1 pro-inflammatory cytokines and downregulation of type 2 anti-inflammatory cytokines. Surprisingly, the cytokine profile was largely unaffected by Na V β4 knockdown in either model. The Na V 1.6 channel, and the Na V β4 subunit that can regulate Na V 1.6 to enhance repetitive firing, play key roles in both models of low back pain; targeting the abnormal spontaneous activity they generate may have therapeutic value.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Role of NaV1.6 and NaVβ4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia

et al. 2019

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“…We tested the MWT of rats at different time points. The results showed that continuous compression of DRG significantly reduced the MWT of the hind paw and was consistent with previous studies [27,28], as shown in Figure 1(b). The MWT decreased significantly on the first day after CCD and reached the lowest point on the 7th day (P < 0:0001).…”

Section: Induction and Persistence Of Allodynia In Ccd Modelsupporting

confidence: 92%

The Wnt/β-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model

Zhang

Zhao

et al. 2021

Neural Plasticity

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Neuropathic pain is one of the important challenges in the clinic. Although a lot of research has been done on neuropathic pain (NP), the molecular mechanism is still elusive. We aimed to investigate whether the Wnt/β-catenin pathway was involved in NP caused by sustaining dorsal root ganglion (DRG) compression with the chronic compression of dorsal root ganglion model (CCD). Our RNA sequencing results showed that several genes related to the Wnt pathway have changed in DRG and spinal cord dorsal horn (SCDH) after CCD surgery. Therefore, we detected the activation of the Wnt/β-catenin pathway in DRG and SCDH and found active β-catenin significantly upregulated in DRG and SCDH 1 day after CCD surgery and peaked on days 7-14. Immunofluorescence results also confirmed nuclear translocalization of active β-catenin in DRG and SCDH. Additionally, rats had obvious mechanical induced pain after CCD surgery and the pain was significantly alleviated after the application of the Wnt/β-catenin pathway inhibitor XAV939. Furthermore, we found that the levels of proinflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were significantly elevated in CCD rat serum, while the levels of them were correspondingly decreased after the Wnt/β-catenin pathway being inhibited. The results of Spearman correlation coefficient analysis showed that the levels of TNF-α and IL-18 were negatively correlated with the mechanical withdrawal thresholds (MWT) after CCD surgery. Collectively, our findings suggest that the Wnt/β-catenin pathway plays a critical role in the pathogenesis of NP and may be an effective target for the treatment of NP.

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“…Synapse-like structures made by sympathetic fibers and dendrites were proved to contribute to the maintenance of chronic pain state [18]. The reduced sprouting produced by early fiber blockage decreased the spontaneous activity of DRG neurons and pain behaviors [43][44][45]. All the previous results were achieved from adult neuropathic pain models.…”

Section: Discussionmentioning

confidence: 95%

“…The sprouting fibers preferentially formed nests with synapse-like structures around the spontaneously active neurons or tangled with efferent fibers [18,42]. The number of sprouting fibers had been proved statistically correlated with neuropathic behaviors [16,43]. Synapse-like structures made by sympathetic fibers and dendrites were proved to contribute to the maintenance of chronic pain state [18].…”

Section: Discussionmentioning

confidence: 99%

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

Liu

Zhang

Gao

et al. 2020

BioMed Research International

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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.

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Inhibition of sympathetic sprouting in CCD rats by lacosamide

Abstract: Early LCM administration inhibited sympathetic sprouting within DRG in CCD rats via reducing hyperexcitability of neurons. Early LCM administration suppressed neuropathic pain in CCD rats.

Cited by 7 publications

References 41 publications

Role of NaV1.6 and NaVβ4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia

Role of NaV1.6 and NaVβ4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia

The Wnt/β-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model

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

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