scholarly journals DTI and MTR Measures of Nerve Fiber Integrity in Pediatric Patients With Ankle Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Scott A. Holmes ◽  
Anastasia Karapanagou ◽  
Steven J. Staffa ◽  
David Zurakowski ◽  
Ronald Borra ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Fiber ◽  
Nerve Injury ◽  
Diffusion Tensor ◽  
Nerve Fibers ◽  
Ankle Injury ◽  
Future Research ◽  
Post Injury ◽  
Fibular Nerve

Acute peripheral nerve injury can lead to chronic neuropathic pain. Having a standardized, non-invasive method to evaluate pathological changes in a nerve following nerve injury would help with diagnostic and therapeutic assessments or interventions. The accurate evaluation of nerve fiber integrity after injury may provide insight into the extent of pathology and a patient's level of self-reported pain. The aim of this investigation was to evaluate the extent to which peripheral nerve integrity could be evaluated in an acute ankle injury cohort and how markers of nerve fiber integrity correlate with self-reported pain levels in afferent nerves. We recruited 39 pediatric participants with clinically defined neuropathic pain within 3 months of an ankle injury and 16 healthy controls. Participants underwent peripheral nerve MRI using diffusion tensor (DTI) and magnetization transfer imaging (MTI) of their injured and non-injured ankles. The imaging window was focused on the branching point of the sciatic nerve into the tibial and fibular division. Each participant completed the Pain Detection Questionnaire (PDQ). Findings demonstrated group differences in DTI and MTI in the sciatic, tibial and fibular nerve in the injured ankle relative to healthy control and contralateral non-injured nerve fibers. Only AD and RD from the injured fibular nerve correlated with PDQ scores which coincides with the inversion-dominant nature of this particular ankle injuruy cohort. Exploratory analyses highlight the potential remodeling stages of nerve injury from neuropathic pain. Future research should emphasize sub-acute time frames of injury to capture post-injury inflammation and nerve fiber recovery.

scholarly journals 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

2015 ◽  
Vol 39 (3) ◽  
pp. E9 ◽  
Author(s):  
Richard B. Boyer ◽  
Nathaniel D. Kelm ◽  
D. Colton Riley ◽  
Kevin W. Sexton ◽  
Alonda C. Pollins ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
High Resolution ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Nerve Fibers ◽  
Nerve Transection ◽  
Nerve Injuries

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

scholarly journals Biological laterality and peripheral nerve DTI metrics

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260256
Author(s):  
Scott A. Holmes ◽  
Steven J. Staffa ◽  
Anastasia Karapanagou ◽  
Natalia Lopez ◽  
Victoria Karian ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Fiber ◽  
Magnetization Transfer ◽  
Mean Diffusivity ◽  
Estimating Equation ◽  
Nerve Fibers ◽  
Equation Modeling ◽  
Main Effect ◽  
Fibular Nerve

Background and purpose Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular). Materials and methods We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed. Results A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles. Conclusion For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients’ recovery and how we forecast pain chronification.

scholarly journals Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

2020 ◽  
Vol 21 (23) ◽  
pp. 9115
Author(s):  
Nathan Moreau ◽  
Yves Boucher
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Hedgehog Signaling ◽  
Future Research ◽  
Chronic Neuropathic Pain ◽  
Desert Hedgehog ◽  
Numerous Cell

The peripheral nervous system has important regenerative capacities that regulate and restore peripheral nerve homeostasis. Following peripheral nerve injury, the nerve undergoes a highly regulated degeneration and regeneration process called Wallerian degeneration, where numerous cell populations interact to allow proper nerve healing. Recent studies have evidenced the prominent role of morphogenetic Hedgehog signaling pathway and its main effectors, Sonic Hedgehog (SHH) and Desert Hedgehog (DHH) in the regenerative drive following nerve injury. Furthermore, dysfunctional regeneration and/or dysfunctional Hedgehog signaling participate in the development of chronic neuropathic pain that sometimes accompanies nerve healing in the clinical context. Understanding the implications of this key signaling pathway could provide exciting new perspectives for future research on peripheral nerve healing.

scholarly journals Diffusion tensor imaging to visualize axons in the setting of nerve injury and recovery

2015 ◽  
Vol 39 (3) ◽  
pp. E10 ◽  
Author(s):  
Thomas Anthony Gallagher ◽  
Neil G. Simon ◽  
Michel Kliot
Keyword(s):  
Diffusion Tensor Imaging ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Diffusion Tensor ◽  
Nerve Fibers ◽  
Accurate Localization ◽  
Peripheral Nerve Trauma ◽  
Nerve Trauma ◽  
Diffusion Tensor Imaging Dti

Successful management of peripheral nerve trauma relies on accurate localization of the injury and grading of the severity of nerve injury to determine whether surgical intervention is required. Existing techniques, such as electrodiagnostic studies and conventional imaging modalities, provide important information, but are limited by being unable to distinguish severe nerve lesions in continuity that will recover from those that will not. Diffusion tensor imaging (DTI) and tractography of peripheral nerves provide a novel technique to localize and grade nerve injury, by assessing the integrity of the nerve fibers across the site of nerve injury. Diffusion tensor imaging and tractography also hold promise as markers of early nerve regeneration, prior to clinical and electrodiagnostic evidence of recovery. In the present review, the techniques of peripheral nerve DTI and tractography are discussed with respect to peripheral nerve trauma, with illustrative cases demonstrating potential roles of these novel approaches.

scholarly journals Visualization of nerve fibers and their relationship to peripheral nerve tumors by diffusion tensor imaging

2015 ◽  
Vol 39 (3) ◽  
pp. E16 ◽  
Author(s):  
Tene A. Cage ◽  
Esther L. Yuh ◽  
Stephanie W. Hou ◽  
Harjus Birk ◽  
Neil G. Simon ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Peripheral Nerve ◽  
Nerve Fiber ◽  
Predictive Value ◽  
Diffusion Tensor ◽  
Retrospective Chart Review ◽  
Nerve Fibers ◽  
Anatomical Location ◽  
Nerve Tumor ◽  
Intraoperative Localization

OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber’s intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach.

scholarly journals SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Thermal Sensitivity ◽  
Gradual Improvement ◽  
Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

scholarly journals Role of the immune system in neuropathic pain

2019 ◽  
Vol 20 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Marzia Malcangio
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Immune Cells ◽  
Peripheral Nerve Injury

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.

376 OLIGONUCLEOTIDE IMT504 REDUCES NEUROPATHIC PAIN AFTER PERIPHERAL NERVE INJURY

2007 ◽  
Vol 11 (S1) ◽  
pp. S167-S167
Author(s):  
M.F. Coronel ◽  
A. Hernando-Insua ◽  
J. Rodriguez ◽  
F. Elias ◽  
J. Flo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury
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