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Peripheral Nerve Injury

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61. Progressive adaptation of whole-limb kinematics after peripheral nerve injury (PubMed)

Progressive adaptation of whole-limb kinematics after peripheral nerve injury The ability to recover purposeful movement soon after debilitating neuromuscular injury is essential to animal survival. Various neural and mechanical mechanisms exist to preserve whole-limb kinematics despite exhibiting long-term deficits of individual joints following peripheral nerve injury. However, it is unclear whether functionally relevant whole-limb movement is acutely conserved following injury. Therefore (...) , the objective of this longitudinal study of the injury response from four individual cats was to test the hypothesis that whole-limb length is conserved following localized nerve injury of ankle extensors in cats with intact nervous systems. The primary finding of our study was that whole-limb kinematics during walking was not immediately preserved following peripheral nerve injuries that paralyzed subsets of ankle extensor muscles. Instead, whole-limb kinematics recovered gradually over multiple weeks

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2018 Biology open

62. Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury (PubMed)

Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury Peripheral nerves are composed of complex layered anatomical structures, including epineurium, perineurium, and endoneurium. Perineurium and endoneurium contain many physical barriers, including the blood-nerve barrier at endoneurial vessels and the perineurial barrier. These physical barriers help to eliminate flux penetration and thus contribute to the establishment of a stable microenvironment. In the current (...) review, we introduce the anatomical compartments and physical barriers of peripheral nerves and then describe the cellular and molecular basis of peripheral physical barriers. We also specifically explore peripheral nerve injury-induced changes of peripheral physical barriers, including elevated endoneurial fluid pressure, increased leakage of tracer, decreased barrier-type endothelial cell ratio, and altered distributions and expressions of cellular junctional proteins. The understanding

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2018 Frontiers in neuroscience

63. Wide-Field Functional Microscopy of Peripheral Nerve Injury and Regeneration (PubMed)

Wide-Field Functional Microscopy of Peripheral Nerve Injury and Regeneration Severe peripheral nerve injuries often result in partial repair and lifelong disabilities in patients. New surgical techniques and better graft tissues are being studied to accelerate regeneration and improve functional recovery. Currently, limited tools are available to provide in vivo monitoring of changes in nerve physiology such as myelination and vascularization, and this has impeded the development of new (...) crush or transection injuries, and in the case of transection, were repaired using an autologous nerve graft or acellular nerve allograft. Such label-free functional imaging by the platform can provide new insights into the mechanisms that limit regeneration and functional recovery, and may ultimately provide intraoperative assessment in human subjects.

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2018 Scientific reports

64. Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury (PubMed)

Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury The neural regeneration process is driven by a wide range of molecules and pathways. Adherens junctions are critical cellular junctions for the integrity of peripheral nerves. However, few studies have systematically characterized the transcript changes in the adherens junction pathway following injury. In this study, a rat model of sciatic nerve crush injury was established by forceps. Deep (...) of these genes were upregulated in the sciatic nerve stump following peripheral nerve injury, except for CTNNA2, which was downregulated. Our findings reveal the dynamic changes of key molecules in adherens junctions and in remodeling of adherens junctions. These key genes provide a reference for the selection of clinical therapeutic targets for peripheral nerve injury.

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2018 Neural Regeneration Research

65. Peripheral Nerve Injury Induces Dynamic Changes of Tight Junction Components (PubMed)

Peripheral Nerve Injury Induces Dynamic Changes of Tight Junction Components Tight junctions seal off physical barriers, regulate fluid and solute flow, and protect the endoneurial microenvironment of the peripheral nervous system. Physical barriers in the peripheral nervous system were disrupted after nerve injury. However, the dynamic changes of tight junction components after peripheral nerve injury have not been fully determined yet. In the current study, by using previously obtained deep (...) sequencing outcomes and bioinformatic tools, we found that tight junction signaling pathway was activated after peripheral nerve injury. The investigation of the temporal expression patterns of components in tight junction signaling pathway suggested that many claudin family members were down-regulated after nerve injury. Moreover, we examined the effects of matrix metalloproteinases 7 and 9 (MMP7 and MMP9) on tight junction genes both in vitro and in vivo and found that MMP7 and MMP9 modulated

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2018 Frontiers in physiology

66. Transcription factor networks involved in cell death in the dorsal root ganglia following peripheral nerve injury (PubMed)

Transcription factor networks involved in cell death in the dorsal root ganglia following peripheral nerve injury The peripheral nervous system has the potential to regenerate after nerve injury owing to the intrinsic regrowth ability of neurons and the permissive microenvironment. The regenerative process involves numerous gene expression changes, in which transcription factors play a critical role. Previously, we profiled dysregulated genes in dorsal root ganglion neurons at different time (...) points (0, 3 and 9 hours, and 1, 4 and 7 days) after sciatic nerve injury in rats by RNA sequencing. In the present study, we investigated differentially expressed transcription factors following nerve injury, and we identified enriched molecular and cellular functions of these transcription factors by Ingenuity Pathway Analysis. This analysis revealed the dynamic changes in the expression of transcription factors involved in cell death at different time points following sciatic nerve injury

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2018 Neural Regeneration Research

67. Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury-associated peripheral sensory neuropathy via block of N- and T-type calcium channels. (PubMed)

Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury-associated peripheral sensory neuropathy via block of N- and T-type calcium channels. The Federal Pain Research Strategy recommended development of nonopioid analgesics as a top priority in its strategic plan to address the significant public health crisis and individual burden of chronic pain faced by >100 million Americans. Motivated by this challenge, a natural product extracts (...) opioid receptors. Intrathecal administration of BA reversed mechanical allodynia in rat models of chemotherapy-induced peripheral neuropathy and HIV-associated peripheral sensory neuropathy as well as a mouse model of partial sciatic nerve ligation without effects on locomotion. The broad-spectrum biological and medicinal properties reported, including anti-HIV and anticancer activities of BA and its derivatives, position this plant-derived small molecule natural product as a potential nonopioid

2018 Pain

68. Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition (PubMed)

Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity (...) the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

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2018 Experimental & molecular medicine

69. Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury (PubMed)

Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential (...) crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation

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2018 Journal of tissue engineering and regenerative medicine

70. The Whole Transcriptome Involved in Denervated Muscle Atrophy Following Peripheral Nerve Injury (PubMed)

The Whole Transcriptome Involved in Denervated Muscle Atrophy Following Peripheral Nerve Injury Peripheral nerve injury (PNI) usually leads to progressive muscle atrophy and poor functional recovery. Previous studies have demonstrated that non-coding ribonucleic acid (ncRNA) is a key regulator of muscle atrophy and beneficial for the treatment of PNI. We aimed to analyze the whole transcriptome involved in denervated muscle atrophy after PNI. Animal models of sciatic nerve injury were assessed (...) at 0 (control group), 1, 2, 4, and 8 weeks after injury. The expression patterns in the whole transcriptome in the gastrocnemius muscle were profiled using RNA sequencing at each time point and compared to that obtained in the control group. Six-hundred and sixty-four long non-coding RNAs, 671 microRNAs, 236 circular RNAs, and 12,768 messenger RNAs (mRNAs) were differentially expressed (DE) after injury. Changes in some of the DE ncRNAs and mRNAs were validated using quantitative polymerase chain

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2018 Frontiers in molecular neuroscience

71. Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system (PubMed)

Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system Spinal cord and peripheral nerve injury results in extensive damage to the locally injured cells as well as distant cells that are functionally connected to them. Both primary and secondary damage can cause a broad range of clinical abnormalities, including neuropathic pain and cognitive and memory dysfunction. However, the mechanisms underlying (...) these abnormalities remain unclear, awaiting new methods to identify affected cells to enable examination of their molecular, cellular and physiological characteristics. Here, we report that both primary and secondary damage to cells in mouse models of spinal cord and peripheral nerve injury can be detected in vivo using a novel fluorescent reporter system based on the immediate stress response via activation of Heat Shock Factor 1. We also provide evidence for altered electrophysiological properties of reporter

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2018 IBRO Reports

72. Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model (PubMed)

Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning (...) the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control) or BoNT/B (5 or 7.5 pg/mouse) into the injured hindpaw. For comparison, another

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2018 Toxins

73. Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury (PubMed)

Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown.Patterns of MMP-9 expression, activity and excretion were assessed in a model (...) of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI.The

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2018 Journal of neuroinflammation

74. Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury. (PubMed)

Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury. Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic (...) constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking

2018 Pain

75. Peripheral nerve injury, scarring, and recovery. (PubMed)

Peripheral nerve injury, scarring, and recovery. Peripheral nerve injuries (PNI) resulting from trauma can be severe and permanently debilitating. Despite the armamentarium of meticulous microsurgical repair techniques that includes direct repair, grafting of defects with autograft nerve, and grafting with cadaveric allografts, approximately one-third of all PNI demonstrate incomplete recovery with poor restoration of function. This may include total loss or incomplete recovery of motor (...) and/or sensory function, chronic pain, muscle atrophy, and profound weakness, which can result in lifelong morbidity. Much of this impaired nerve healing can be attributed to perineural scarring and fibrosis at the site of injury and repair. To date, this challenging clinical problem has not been adequately addressed. In this review, we summarize the existing literature surrounding biological aspects of perineural fibrosis following PNI, detail current strategies to limit nerve scarring, present our own work

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2018 Connective Tissue Research

76. A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery. (PubMed)

A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery. Peripheral nerve injury is a potentially devastating complication after total shoulder arthroplasty (TSA) surgery. This pilot study aimed to assess the feasibility of using an automated somatosensory evoked potential (SSEP) device to provide a timely alert/intervention to minimize intraoperative (...) insults. No patients demonstrated postoperative peripheral neuropathy at 6 weeks.A high incidence (19%) of intraoperative nerve insult was observed in this study demonstrating the feasibility of using an automated SSEP device to provide a timely alert and enable an intervention in order to minimize peripheral nerve injury during TSA. Further randomized studies are warranted.

2018 Journal of neurosurgical anesthesiology

77. Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. (PubMed)

Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed (...) -10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats. Finally, in cultured DRG neurons, Cav2.2 was dose-dependently upregulated by IL-1β and downregulated by IL-10. These data indicate that the upregulation of Cav2.2 in uninjured DRG neurons via IL-1β over-production contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.Copyright © 2018 Elsevier Inc. All rights reserved.

2018 Brain, behavior, and immunity

78. Perioperative Peripheral Nerve Injury After General Anesthesia: A Qualitative Systematic Review. (PubMed)

Perioperative Peripheral Nerve Injury After General Anesthesia: A Qualitative Systematic Review. Perioperative peripheral nerve injury (PNI) is a well-recognized complication of general anesthesia that continues to result in patient disability and malpractice claims. However, the multifactorial etiology of PNI is often not appreciated in malpractice claims given that most PNI is alleged to be due to errors in patient positioning. New advances in monitoring may aid anesthesiologists in the early (...) and ulnar nerves representing two-thirds of PNI claims. The causes of perioperative PNI after general anesthesia are likely multifactorial, resulting in a "difficult to predict and prevent" phenomenon. Nearly half of the PNI closed claims did not have an obvious etiology, and most (91%) were associated with appropriate anesthetic care. Future studies should focus on the interaction between different mechanisms of insult, severity and duration of injury, and underlying neuronal reserves. Recent automated

2018 Anesthesia and Analgesia

79. CRACKCast 107 – Peripheral Nerve Disorders

Asymmetrical proximal and distal peripheral neuropathies: Brachial plexopathy Open Direct plexus injury (knife or gunshot wound) Neurovascular (plexus ischemia) Iatrogenic (central line insertion) Closed Traction injuries “Stingers” Traction neurapraxia Partial or complete nerve root avulsion Radiation Neoplastic Idiopathic brachial plexitis Thoracic outlet Lumbosacral plexopathies Open Closed Traction injuries Pelvic double vertical shearing fracture Posterior hip dislocation Retroperitoneal hemorrhage (...) CRACKCast 107 – Peripheral Nerve Disorders CRACKCast 107 - Peripheral Nerve Disorders - CanadiEM CRACKCast 107 – Peripheral Nerve Disorders In , by Chris Lipp September 7, 2017 This episode of CRACKCast covers Rosen’s Chapter 107, Peripheral Nerve Disorders. These disorders have a wide range of presentations and etiologies. This chapter includes a comprehensive classification system to help in the ED in recognizing the various disorders. Shownotes – Rosen’s In Perspective Nervous System

2017 CandiEM

80. Ultrasound-guided percutaneous peripheral nerve stimulation: neuromodulation of the suprascapular nerve and brachial plexus for postoperative analgesia following ambulatory rotator cuff repair. A proof-of-concept study. (PubMed)

Ultrasound-guided percutaneous peripheral nerve stimulation: neuromodulation of the suprascapular nerve and brachial plexus for postoperative analgesia following ambulatory rotator cuff repair. A proof-of-concept study. Percutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducing needle followed by the delivery of electric current. This modality has been reported to treat chronic pain as well as postoperative pain following (...) -14 had a median of 1 or less on the Numeric Rating Scale, and opioid requirements averaged less than 1 tablet daily with active stimulation. Two leads dislodged during use and four fractured on withdrawal, but no infections, nerve injuries, or adverse sequelae were reported.This proof-of-concept study demonstrates that ultrasound-guided percutaneous PNS of the brachial plexus is feasible for ambulatory shoulder surgery, and although analgesia immediately following surgery does not appear

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2019 Regional Anesthesia and Pain Medicine

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