Cervical spinal cord injury-induced neuropathic pain in male mice is associated with a persistent pro-inflammatory macrophage/microglial response in the superficial dorsal horn

2021 ◽  
pp. 113757
Author(s):  
Eric V. Brown ◽  
Aditi Falnikar ◽  
Nicolette Heinsinger ◽  
Lan Cheng ◽  
Carrie E. Andrews ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Cervical Spinal Cord ◽  
Superficial Dorsal Horn ◽  
Male Mice ◽  
Cord Injury ◽  
Microglial Response ◽  
Inflammatory Macrophage

scholarly journals Beneficial Effects of Electroacupuncture on Neuropathic Pain Evoked by Spinal Cord Injury and Involvement of PI3K-mTOR Mechanisms

2018 ◽  
Vol 21 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Yujie Wang ◽  
Yu Zhao ◽  
Xiaohui Ma ◽  
Jing Li ◽  
Junling Hou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Molecular Mechanisms ◽  
Mtor Signaling ◽  
Superficial Dorsal Horn ◽  
Beneficial Effects ◽  
Thermal Pain ◽  
Cord Injury

The purpose of this study was to examine the beneficial effects of electroacupuncture (EA) on neuropathic pain evoked by spinal cord injury (SCI) and determine the underlying molecular mechanisms of these effects. SCI was induced in rats. Behavioral tests were performed to examine pain responses induced by mechanical and thermal stimulation. Western blot analysis was used to measure the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR), mTOR-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p-S6K1), and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1) in the superficial dorsal horn of the spinal cord. We showed that SCI increased the expression of p-mTOR, p-S6K1, and p-4E-BP1. The EA intervention attenuated the upregulation of mTOR signaling and alleviated mechanical and thermal pain responses in SCI rats. Blocking spinal mTOR by intrathecal injection of rapamycin also inhibited mechanical and thermal pain. In addition, blocking spinal phosphorylated phosphatidylinositide 3-kinase (p-PI3K) pathway attenuated p-mTOR pathways and mechanical and thermal hyperalgesia in SCI rats. EA also decreased the enhanced p-PI3K in the superficial dorsal horn of SCI rats. In conclusion, findings revealed specific signaling pathways that lead to neuropathic pain in response to SCI, including activation of PI3K-mTOR signaling. Further, results link the beneficial role of EA in alleviating SCI-induced neuropathic pain to its effect on these molecular mechanisms.

scholarly journals Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury

2020 ◽  
Vol 334 ◽  
pp. 113468
Author(s):  
Nicolette M. Heinsinger ◽  
Gabrielle Spagnuolo ◽  
R. Vivian Allahyari ◽  
Simon Galer ◽  
Tyler Fox ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Mouse Model ◽  
Cervical Spinal Cord ◽  
Cervical Spinal Cord Injury ◽  
Cord Injury

scholarly journals Dendritic spine dysgenesis in superficial dorsal horn sensory neurons after spinal cord injury

2017 ◽  
Vol 13 ◽  
pp. 174480691668801 ◽  
Author(s):  
Xiaoyu C Cao ◽  
Laura W Pappalardo ◽  
Stephen G Waxman ◽  
Andrew M Tan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Dorsal Horn ◽  
Sensory Neurons ◽  
Dendritic Spine ◽  
Superficial Dorsal Horn ◽  
Cord Injury

scholarly journals Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoping Wang ◽  
Xiaojia Li ◽  
Bin Huang ◽  
Shuai Ma
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Dorsal Horn ◽  
Intrathecal Injection ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

scholarly journals Investigating resting-state functional connectivity in the cervical spinal cord at 3T

2016 ◽  
Author(s):  
Falk Eippert ◽  
Yazhuo Kong ◽  
Anderson M. Winkler ◽  
Jesper L. Andersson ◽  
Jürgen Finsterbusch ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Dorsal Horn ◽  
Resting State ◽  
High Field ◽  
Cervical Spinal Cord ◽  
Ventral Horn ◽  
Ultra High Field ◽  
Cord Injury ◽  
Resting State Connectivity

AbstractThe study of spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord. Two ultra-high field functional magnetic resonance imaging (fMRI) studies in humans have provided evidence for reproducible resting-state connectivity between the dorsal horns as well as between the ventral horns, and a study in non-human primates has shown that these resting-state signals are impacted by spinal cord injury. As these studies were carried out at ultra-high field strengths using region-of-interest (ROI) based analyses, we investigated whether such resting-state signals could also be observed at the clinically more prevalent field strength of 3T. In a reanalysis of a sample of 20 healthy human participants who underwent a resting-state fMRI acquisition of the cervical spinal cord, we were able to observe significant dorsal horn connectivity as well as ventral horn connectivity, but no consistent effects for connectivity between dorsal and ventral horns, thus replicating the human 7T results. These effects were not only observable when averaging along the acquired length of the spinal cord, but also when we examined each of the acquired spinal segments separately, which showed similar patterns of connectivity. Finally, we investigated the robustness of these resting-state signals against variations in the analysis pipeline by varying the type of ROI creation, temporal filtering, nuisance regression and connectivity metric. We observed that – apart from the effects of band-pass filtering – ventral horn connectivity showed excellent robustness, whereas dorsal horn connectivity showed moderate robustness. Together, our results provide evidence that spinal cord resting-state connectivity is a robust and spatially consistent phenomenon that could be a valuable tool for investigating the effects of pathology, disease progression, and treatment response in neurological conditions with a spinal component, such as spinal cord injury.

Sign in / Sign up

Export Citation Format

Share Document