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Beth A Winkelstein - One of the best experts on this subject based on the ideXlab platform.

  • the roles of mechanical compression and chemical irritation in regulating spinal neuronal signaling in painful Cervical Nerve Root injury
    Stapp car crash journal, 2013
    Co-Authors: Sijia Zhang, Kristen J Nicholson, Jenell R Smith, Taylor M Gilliland, Peter Syre, Beth A Winkelstein
    Abstract:

    Both traumatic and slow-onset disc herniation can directly compress and/or chemically irritate Cervical Nerve Roots, and both types of Root injury elicit pain in animal models of radiculopathy. This study investigated the relative contributions of mechanical compression and chemical irritation of the Nerve Root to spinal regulation of neuronal activity using several outcomes. Modifications of two proteins known to regulate neurotransmission in the spinal cord, the neuropeptide calcitonin gene-related peptide (CGRP) and glutamate transporter 1 (GLT-1), were assessed in a rat model after painful Cervical Nerve Root injuries using a mechanical compression, chemical irritation or their combination of injury. Only injuries with compression induced sustained behavioral hypersensitivity (p≤0.05) for two weeks and significant decreases (p<0.037) in CGRP and GLT-1 immunoreactivity to nearly half that of sham levels in the superficial dorsal horn. Because modification of spinal CGRP and GLT-1 is associated with enhanced excitatory signaling in the spinal cord, a second study evaluated the electrophysiological properties of neurons in the superficial and deeper dorsal horn at day 7 after a painful Root compression. The evoked firing rate was significantly increased (p=0.045) after compression and only in the deeper lamina. The painful compression also induced a significant (p=0.002) shift in the percentage of neurons in the superficial lamina classified as low- threshold mechanoreceptive (sham 38%; compression 10%) to those classified as wide dynamic range neurons (sham 43%; compression 74%). Together, these studies highlight mechanical compression as a key modulator of spinal neuronal signaling in the context of radicular injury and pain.

  • the potential for salmon fibrin and thrombin to mitigate pain subsequent to Cervical Nerve Root injury
    Biomaterials, 2011
    Co-Authors: Christine L Weisshaar, Jessamine P Winer, Benjamin B Guarino, Paul A Janmey, Beth A Winkelstein
    Abstract:

    Nerve Root compression is a common cause of radiculopathy and induces persistent pain. Mammalian fibrin is used clinically as a coagulant but presents a variety of risks. Fish fibrin is a potential biomaterial for neural injury treatment because it promotes neurite outgrowth, is non-toxic, and clots readily at lower temperatures. This study administered salmon fibrin and thrombin following Nerve Root compression and measured behavioral sensitivity and glial activation in a rat pain model. Fibrin and thrombin each significantly reduced mechanical allodynia compared to injury alone (p < 0.02). Painful compression with fibrin exhibited allodynia that was not different from sham for any day using stimulation by a 2 g filament; allodynia was only significantly different (p < 0.043) from sham using the 4 g filament on days 1 and 3. By day 5, responses for fibrin treatment decreased to sham levels. Allodynia following compression with thrombin treatment were unchanged from sham at any time point. Macrophage infiltration at the Nerve Root and spinal microglial activation were only mildly modified by salmon treatments. Spinal astrocytic expression decreased significantly with fibrin (p < 0.0001) but was unchanged from injury responses for thrombin treatment. Results suggest that salmon fibrin and thrombin may be suitable biomaterials to mitigate pain.

  • cytokine antagonism reduces pain and modulates spinal astrocytic reactivity after Cervical Nerve Root compression
    Annals of Biomedical Engineering, 2010
    Co-Authors: Sarah M Rothman, Beth A Winkelstein
    Abstract:

    Relationships between Nerve Root compression, behavioral sensitivity, spinal cytokines, and glial reactivity are not fully defined for painful Cervical Nerve Root compression. Spinal cytokines were quantified after mechanical Root compression (10gf), Root exposure to inflammatory chromic gut material (chr), the combination of both insults together (10gf + chr) or sham. TNFα and IL-1β significantly increased at 1 h (p < 0.029). IL-1α was significantly increased over normal, sham and chr at 1 h following 10gf and over normal and sham after 10gf + chr (p < 0.048). By day 1, only IL-1β after 10gf remained elevated over normal (p = 0.038). Accordingly, the soluble TNF receptor-1 (sTNFR1) and the IL-1 receptor antagonist (IL-1ra) were separately administered at early time points after each injury. With sTNFR1, behavioral sensitivity was significantly decreased for 7 days after both 10gf and 10gf + chr (p < 0.005). Treatment with IL-1ra significantly reduced sensitivity for 10gf + chr (p < 0.034) but not for 10gf. Sensitivity remained significantly elevated over sham at all time points (p < 0.044). Spinal astrocytic reactivity significantly decreased for both treatments after 10gf (p < 0.002); but, only IL-1ra following 10gf + chr significantly reduced astrocytic reactivity (p < 0.001). Early increases in spinal TNFα, IL-1β, and IL-1α may induce pain, affect spinal astrocytic responses, and appear to have differential effects in mediating the behavioral hypersensitivity produced by different types of painful Cervical radicular injuries.

  • cytokine mrna expression in painful radiculopathy
    The Journal of Pain, 2009
    Co-Authors: Sarah M Rothman, Christine L Weisshaar, Zhong Huang, Beth A Winkelstein
    Abstract:

    Abstract Inflammatory cytokines contribute to lumbar radiculopathy. Regulation of cytokines for transient Cervical injuries, with or without longer-lasting inflammation, remains to be defined. The C7 Root in the rat underwent compression (10gf), chromic gut suture exposure (chr), or their combination (10gf+chr). Ipsilateral C7 spinal cord and dorsal Root ganglia (DRG) were harvested at 1 hour after injury for real-time PCR analysis of IL-1β, IL-6, and TNF-α. Cytokine mRNA increased after all 3 injuries. TNF-α mRNA in the DRG was significantly increased over sham after 10gf+chr ( P = .026). Spinal IL-1β was significantly increased over sham after 10gf and 10gf+chr ( P P P P Perspective Inflammatory cytokine mRNA in the DRG and spinal cord are defined after painful Cervical Nerve Root injury. Studies describe a role for TNF-α in mediating behavioral sensitivity and inflammatory cytokines in transient painful radiculopathy. Results outline an early response of inflammatory cytokine upregulation in Cervical pain.

  • transient Cervical Nerve Root compression modulates pain load thresholds for allodynia and sustained changes in spinal neuropeptide expression
    Journal of Biomechanics, 2008
    Co-Authors: Raymond D Hubbard, Zhen Chen, Beth A Winkelstein
    Abstract:

    Nerve Root compression produces chronic pain and altered spinal neuropeptide expression. This study utilized controlled transient loading in a rat model of painful Cervical Nerve Root compression to investigate the dependence of mechanical allodynia on load magnitude. Injury loads (0-110mN) were applied quasistatically using a customized loading device, and load thresholds to produce maintained mechanical allodynia were defined. Bilateral spinal expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed 7 days following compression using immunohistochemistry to determine relationships between these neuropeptides and compression load. A three-segment change point model was implemented to model allodynia responses and their relationship to load. Load thresholds were defined at which ipsilateral and contralateral allodynia were produced and sustained. The threshold for increased allodynia was lowest for acute (day 1) ipsilateral responses (26.29mN), while thresholds for allodynia on day 7 were similar for the ipsilateral (38.16mN) and contralateral forepaw (38.26mN). CGRP, but not SP, significantly decreased with load; the thresholds for ipsilateral and contralateral CGRP decreases corresponded to 19.52 and 24.03mN, respectively. These thresholds suggest bilateral allodynia may be mediated by spinal mechanisms, and that these mechanisms depend on the magnitude of load.

Raymond D Hubbard - One of the best experts on this subject based on the ideXlab platform.

  • transient Cervical Nerve Root compression modulates pain load thresholds for allodynia and sustained changes in spinal neuropeptide expression
    Journal of Biomechanics, 2008
    Co-Authors: Raymond D Hubbard, Zhen Chen, Beth A Winkelstein
    Abstract:

    Nerve Root compression produces chronic pain and altered spinal neuropeptide expression. This study utilized controlled transient loading in a rat model of painful Cervical Nerve Root compression to investigate the dependence of mechanical allodynia on load magnitude. Injury loads (0-110mN) were applied quasistatically using a customized loading device, and load thresholds to produce maintained mechanical allodynia were defined. Bilateral spinal expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed 7 days following compression using immunohistochemistry to determine relationships between these neuropeptides and compression load. A three-segment change point model was implemented to model allodynia responses and their relationship to load. Load thresholds were defined at which ipsilateral and contralateral allodynia were produced and sustained. The threshold for increased allodynia was lowest for acute (day 1) ipsilateral responses (26.29mN), while thresholds for allodynia on day 7 were similar for the ipsilateral (38.16mN) and contralateral forepaw (38.26mN). CGRP, but not SP, significantly decreased with load; the thresholds for ipsilateral and contralateral CGRP decreases corresponded to 19.52 and 24.03mN, respectively. These thresholds suggest bilateral allodynia may be mediated by spinal mechanisms, and that these mechanisms depend on the magnitude of load.

  • transient Cervical Nerve Root compression in the rat induces bilateral forepaw allodynia and spinal glial activation mechanical factors in painful neck injuries
    Spine, 2005
    Co-Authors: Raymond D Hubbard, Beth A Winkelstein
    Abstract:

    STUDY DESIGN An in vivo rat model of transient Cervical Nerve Root compression. OBJECTIVES To investigate the potential for Cervical Nerve Root compression to produce behavioral hypersensitivity and examine its dependence on compression. SUMMARY OF BACKGROUND DATA Clinically, Nerve Root injury has been hypothesized as a potential source of neck pain, particularly because Cervical Nerve Roots are at mechanical risk for injury during neck loading. Lumbar radiculopathy models of Nerve Root ligation show that mechanical allodynia and spinal glial changes depend on Nerve Root deformation magnitude. However, no investigation has been performed to examine Cervical Nerve Root compression as a cause of pain. METHODS Two compressive forces (10 and 60 grams force [gf]) were transiently applied to the C7 Nerve Roots unilaterally using microvascular clips in separate groups (n = 12 each). Sham procedures were also performed in a separate group of rats (n = 12). Bilateral forepaw mechanical allodynia was monitored after surgery for 7 days. On day 7, spinal glial activation was assessed using immunohistochemistry to investigate its dependence on Nerve Root compressive force, in the context of behavioral hypersensitivity. RESULTS Bilateral allodynia was observed following injury, which was significantly (P < 0.042) increased over sham and baseline responses. No difference in allodynia was found between the 10 and 60 gf injuries. Astrocytic and microglial activation were observed in the ipsilateral dorsal horn following compression, with only astrocytic activation paralleling allodynia patterns. CONCLUSIONS Results imply a force threshold exists less than 10 gf for persistent pain symptoms following transient Cervical Nerve Root compression. Findings also suggest that spinal glial activation may be related to behavioral sensitivity and may modulate Cervical Nerve Root mediated pain.

Joon Shik Yoon - One of the best experts on this subject based on the ideXlab platform.

  • ultrasound guided Cervical Nerve Root block does volume affect the spreading pattern
    Pain Medicine, 2016
    Co-Authors: Seok Ho Kang, Seung Nam Yang, Se Hwa Kim, Chan Woo Byun, Joon Shik Yoon
    Abstract:

    Objective . Ultrasound-guided Cervical Nerve Root block (US-CRB) is considered a safe and effective method for the treatment of radicular pain. However, previous studies on the spreading pattern of injected solution in US-CRB have reported conflicting results. The aim of this study was to investigate the spreading pattern in relation to injection volume. Design . An institutional, prospective case series. Setting . A university hospital. Subjects . Fifty-three patients diagnosed with mono-radiculopathy in C5, 6, or 7. Methods . US-CRB with fluoroscopic confirmation was performed. After the Cervical Roots were identified in ultrasound imaging, a needle was gently introduced toward the posterior edge of the Root using an in-plane approach. The spread of 1 mL and 4 mL contrast medium, each injected in the same needle position, was examined with anteroposterior and lateral fluoroscopic views. After contrast injection, a mixture of local anesthetic and corticosteroid was injected. Clinical outcome was assessed using a numeric rating scale before and 2 weeks after the procedure. Results . Contrast medium did not spread into the epidural space in any patients with 1 mL contrast medium injection, but it did spread into the intraforaminal epidural space in 13 patients (24.5%) with 4 mL. Pain improved in all patients. There was no significant difference in pain relief according to the spreading pattern. Conclusion . The spreading pattern of injected solution in US-CRB could be partially affected by the injectant volume. However, further studies are needed to assess the importance of other factors, such as needle position and physiological effects.

  • ultrasound guided lower Cervical Nerve Root injectate volumes associated with dorsal Root ganglion and epidural spread
    Journal of Ultrasound in Medicine, 2016
    Co-Authors: Sun Jae Won, Won Ihl Rhee, Joon Shik Yoon, Uyoung Lee
    Abstract:

    Objectives We aimed to estimate the spread of injections for ultrasound-guided Cervical Nerve Root blocks and to determine the optimal injectate volume required in this procedure. Methods A total of 32 ultrasound-guided injections (C5–C8) were made in 4 fresh cadavers. The target on each Cervical Root was the space between the posterior tubercle and the Cervical Root at the most proximal location possible on the sonogram. After ultrasound-guided needle insertion, 0.5 mL of a contrast medium was injected 4 times. The dye flow patterns were confirmed with fluoroscopy each time, and we recorded whether the contrast medium reached the dorsal Root ganglion level or the epidural space. After the injections, the needle tip location was determined by computed tomography and image reconstruction. Results All injections produced typical neurograms. The contrast medium reached the dorsal Root ganglion in 29 of 32 (90.6%) injections (mean ± SD, 0.84 ± 0.42 mL of contrast medium) and the epidural space in 10 of 32 (31.3%) injections (1.30 ± 0.54 mL of contrast medium). The mean distance between the needle tip and neural foramen was 9.64 ± 3.68 mm, and this distance correlated positively with the volume of contrast medium necessary to reach the dorsal Root ganglion or the epidural space. Conclusions Ultrasound-guided Cervical Nerve Root blocks show potential utility for targeting an anesthetic into the Cervical Root area. This study may be helpful for deciding the most appropriate volume for the procedure.

Woo Jin Choe - One of the best experts on this subject based on the ideXlab platform.

Hubertus Axer - One of the best experts on this subject based on the ideXlab platform.

  • ultrasonography of the peripheral nervous system in vasculitic neuropathies
    Clinical Neurophysiology, 2016
    Co-Authors: Alexander Grimm, Antje Bischof, Bernhard F. Décard, Hubertus Axer
    Abstract:

    Introduction Ultrasound of the peripheral Nerves (PNUS) is used to visualize Nerve pathologies in polyneuropathies (PNP). Aim of this study was to investigate, whether PNUS provides additional information in patients with proven systemic vasculitic neuropathies (VN). Material and methods Systematic ultrasound of several peripheral Nerves, the vagal Nerve and the 6th Cervical Nerve Root was performed in 14 patients and 22 healthy controls. The measured results were compared to a study population of demyelinating immune-mediated and axonal neuropathies. Results Patients with VN displayed significant smaller amplitudes of compound muscle action potentials (CMAP) ( p p Conclusion Focal CSA enlargement in one or more Nerves in electrophysiologically axonal neuropathies can be a hint for VN and thus facilitate diagnostic and therapeutic procedures.

  • Ultrasound of the peripheral Nerves in systemic vasculitic neuropathies
    Journal of the Neurological Sciences, 2014
    Co-Authors: Alexander Grimm, Antje Bischof, Bernhard F. Décard, Hubertus Axer
    Abstract:

    INTRODUCTION: Ultrasound of the peripheral Nerves (PNUS) can be used to visualize Nerve pathologies in polyneuropathies (PNP). The aim of this study was to investigate, whether PNUS provides additional information in patients with proven systemic vasculitic neuropathies (VN). MATERIAL AND METHODS: Systematic ultrasound measurements of several peripheral Nerves, the vagal Nerve and the 6th Cervical Nerve Root were performed in 14 patients and 22 healthy controls. Nerve conduction studies of the corresponding Nerves were undertaken. Finally, the measured results were compared to a study population of demyelinating immune-mediated and axonal neuropathies. RESULTS: Patients with VN displayed significant smaller amplitudes of compound muscle action potentials (CMAP) (p