scholarly journals Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Javier Sábado ◽  
Anna Casanovas ◽  
Olga Tarabal ◽  
Marta Hereu ◽  
Lídia Piedrafita ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Ventral Horn ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Cord Dorsal ◽  
Neuronal Types ◽  
Misfolded Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations ofsuperoxide dismutase 1(SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used theSOD1G93Amouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

scholarly journals Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jussi Kupari ◽  
Dmitry Usoskin ◽  
Marc Parisien ◽  
Daohua Lou ◽  
Yizhou Hu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Species Conservation ◽  
Cell Types ◽  
Individual Gene ◽  
Cellular Origin ◽  
Neuronal Types

AbstractDistinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.

358 UP-REGULATION OF MICRORNA-16 IN THE DORSAL ROOT GANGLION AND SPINAL CORD DORSAL HORN FOLLOWING PERIPHERAL NERVE INJURY

2007 ◽  
Vol 11 (S1) ◽  
pp. S158-S159
Author(s):  
R. Kusuda ◽  
S. Zanon ◽  
T. Amaral E. Souza ◽  
F. Cadetti ◽  
N. Zanon-Baptista ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root Ganglion ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Dorsal Root ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Cord Dorsal

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

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ye Zhang ◽  
Dan Zhao ◽  
Xutong Li ◽  
Beiyao Gao ◽  
Chengcheng Sun ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Critical Role ◽  
Spinal Cord Dorsal Horn ◽  
Rat Serum ◽  
Tnf Α ◽  
Spinal Cord Dorsal ◽  
Factor Α ◽  
Necrosis Factor

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.

scholarly journals A Rat Model of Radicular Pain Induced by Chronic Compression of Lumbar Dorsal Root Ganglion with SURGIFLO ™

2008 ◽  
Vol 108 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Xiaoping Gu ◽  
Liling Yang ◽  
Shuxing Wang ◽  
Backil Sung ◽  
Grewo Lim ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Rat Model ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Radicular Pain ◽  
Spinal Cord Dorsal Horn ◽  
Aspartate Receptor ◽  
Spinal Cord Dorsal ◽  
Lumbar Dorsal Root Ganglion

Background Radicular pain is a common and debilitating clinical pain condition. To date, the mechanisms of radicular pain remain unclear, partly because of the lack of suitable preclinical models. The authors report a modified rat model of radicular pain that could mimic a subset of clinical radicular pain conditions induced by the soft tissue compression on dorsal root ganglion. Methods A rat model of radicular pain was produced by infiltrating the L5 intervertebral foramen with 60 microl of a hemostatic matrix (SURGIFLO; Johnson & Johnson, Somerville, NJ) resulting in chronic compression of lumbar dorsal root ganglion. Thermal hyperalgesia and mechanical allodynia were measured with or without epidural treatment with triamcinolone. Western blot was used to assess the expression of the NR1 subunit of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha, an inflammatory marker, within the affected L5 dorsal root ganglion and spinal cord dorsal horn. Results Chronic compression of lumbar dorsal root ganglion resulted in: (1) persistent mechanical allodynia and thermal hyperalgesia up to 4 or 5 postoperative weeks and (2) up-regulation of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha within the ipsilateral L5 dorsal root ganglion and spinal cord dorsal horn. Epidural administration of triamcinolone (6.25-100 microg) on postoperative day 3 dose-dependently attenuated both thermal hyperalgesia and mechanical allodynia in rats with chronic compression of lumbar dorsal root ganglion. Conclusion The data suggest that this modified rat model of chronic compression of lumbar dorsal root ganglion may be a useful tool to explore the mechanisms as well as new therapeutic options of radicular pain.

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