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Beth A Winkelstein - One of the best experts on this subject based on the ideXlab platform.
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Nerve Root Compression Increases Spinal Astrocytic Vimentin in Parallel With Sustained Pain and Endothelial Vimentin in Association With Spinal Vascular Reestablishment.
Spine, 2017Co-Authors: Jenell R. Smith, Jasmine Lee, Beth A WinkelsteinAbstract:Study Design.Temporal immunohistochemistry analysis of spinal cord tissue from a rat model of cervical radiculopathy.Objective.The goal was to measure spinal endothelial and astrocytic vimentin expression after a painful Nerve Root Compression to define spinal cellular expression of vimentin in the
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transient Nerve Root Compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mglur5 expression
Neuroscience, 2012Co-Authors: Kristen J Nicholson, Benjamin B Guarino, Beth A WinkelsteinAbstract:Injury to the cervical Nerve Roots is a common source of neck pain. Animal models of Nerve Root Compression have previously established the role of Compression magnitude and duration in Nerve Root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient Nerve Root Compression and its relationship to Compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following Nerve Root Compressions of different magnitudes and durations in the rat. Compression to the C7 Nerve Root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during Compression. To also test for the effect of the magnitude of the Compression load, either a 10 gf or a 60 gf was applied to the Nerve Root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of Compression produced significantly greater behavioral sensitivity (P<0.001) and spinal GFAP expression (P=0.002) than 3 min of Compression, regardless of the Compression magnitude. Nerve Root Compression at 60 gf produced a significant increase (P<0.001) in spinal mGluR5 for both of the durations studied. There was no difference in the distribution of mGluR5 between astrocytes and neurons following Nerve Root Compression of any type. The glutamatergic and glial systems are differentially modulated by the mechanics of Nerve Root Compression despite the known contribution of glia to pain through glutamatergic signaling.
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Transient Nerve Root Compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGLuR5 expression.
Neuroscience, 2012Co-Authors: Kristen J Nicholson, Benjamin B Guarino, Beth A WinkelsteinAbstract:Injury to the cervical Nerve Roots is a common source of neck pain. Animal models of Nerve Root Compression have previously established the role of Compression magnitude and duration in Nerve Root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient Nerve Root Compression and its relationship to Compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following Nerve Root Compressions of different magnitudes and durations in the rat. Compression to the C7 Nerve Root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during Compression. To also test for the effect of the magnitude of the Compression load, either a 10 gf or a 60 gf was applied to the Nerve Root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of Compression produced significantly greater behavioral sensitivity (P
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Development of a Duration Threshold for Modulating Evoked Neuronal Responses After Nerve Root Compression Injury
Stapp car crash journal, 2011Co-Authors: Kristen J Nicholson, Julia C. Quindlen, Beth A WinkelsteinAbstract:Cervical Nerve Roots are susceptible to Compression injuries of various durations. The duration of an applied Compression has been shown to contribute to both the onset of persistent pain and also the degree of spinal cellular and molecular responses related to nociception. This study investigated the relationship between peripherally-evoked activity in spinal cord neurons during a Root Compression and the resulting development of axonal damage. Electrically-evoked spikes were measured in the spinal cord as a function of time during and after (post-Compression) a 15 minute Compression of the C7 Nerve Root. Compression to the Root significantly (p=0.035) reduced the number of spikes that were evoked over time relative to sham. The critical time for Compression to maximally reduce evoked spikes was 6.6±3.0 minutes. A second study measured the post- Compression evoked neuronal activity following Compression applied for a shorter, sub-threshold time (three minutes). Ten minutes after Compression was removed, the discharge rate remained significantly (p=0.018) less than baseline by 58±25% relative to sham after the 15 minute Compression, but returned to within 3±33% of baseline after the three minute Compression. Axonal damage was evident in the Nerve Root at day seven after Nerve Root Compression only after a 15 minute Compression. These studies demonstrate that even a transient mechanical insult to the Nerve Root is sufficient to induce sustained neuronal dysfunction and axonal pathology associated with pain, and results provide support that such minor neural tissue traumas can actually induce long-lasting functional deficits.
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The Duration of a Nerve Root Compression Modulates Evoked Neuronal Responses in a Rat Model of Painful Injury
ASME 2011 Summer Bioengineering Conference Parts A and B, 2011Co-Authors: Kristen J Nicholson, Beth A WinkelsteinAbstract:The annual incidence for neck pain in the adult population is 30–50% [1]. The cervical Nerve Roots are at risk for mechanical injury due to impingement of surrounding structures which can result in pain and numbness [2]. During Nerve Root Compression, an immediate, brief increase in spontaneous afferent activity and a gradual decrease in electrically evoked axonal conduction have been reported [3,4]. Although previous studies demonstrate that a transient cervical Nerve Root Compression induces persistent behavioral sensitivity [5,6], it is not known how the tissue mechanics during loading modulate neuronal function or how they relate to the onset of pain. Therefore, the goal of this study was to quantify neuronal activity in the spinal cord as a function of the duration of applied Compression by measuring both electrically-evoked and spontaneous afferent activity during a transient Compression of the cervical Nerve Root in a rat model of pain [5,6].Copyright © 2011 by ASME
Kristen J Nicholson - One of the best experts on this subject based on the ideXlab platform.
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transient Nerve Root Compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mglur5 expression
Neuroscience, 2012Co-Authors: Kristen J Nicholson, Benjamin B Guarino, Beth A WinkelsteinAbstract:Injury to the cervical Nerve Roots is a common source of neck pain. Animal models of Nerve Root Compression have previously established the role of Compression magnitude and duration in Nerve Root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient Nerve Root Compression and its relationship to Compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following Nerve Root Compressions of different magnitudes and durations in the rat. Compression to the C7 Nerve Root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during Compression. To also test for the effect of the magnitude of the Compression load, either a 10 gf or a 60 gf was applied to the Nerve Root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of Compression produced significantly greater behavioral sensitivity (P<0.001) and spinal GFAP expression (P=0.002) than 3 min of Compression, regardless of the Compression magnitude. Nerve Root Compression at 60 gf produced a significant increase (P<0.001) in spinal mGluR5 for both of the durations studied. There was no difference in the distribution of mGluR5 between astrocytes and neurons following Nerve Root Compression of any type. The glutamatergic and glial systems are differentially modulated by the mechanics of Nerve Root Compression despite the known contribution of glia to pain through glutamatergic signaling.
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Transient Nerve Root Compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGLuR5 expression.
Neuroscience, 2012Co-Authors: Kristen J Nicholson, Benjamin B Guarino, Beth A WinkelsteinAbstract:Injury to the cervical Nerve Roots is a common source of neck pain. Animal models of Nerve Root Compression have previously established the role of Compression magnitude and duration in Nerve Root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient Nerve Root Compression and its relationship to Compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following Nerve Root Compressions of different magnitudes and durations in the rat. Compression to the C7 Nerve Root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during Compression. To also test for the effect of the magnitude of the Compression load, either a 10 gf or a 60 gf was applied to the Nerve Root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of Compression produced significantly greater behavioral sensitivity (P
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Development of a Duration Threshold for Modulating Evoked Neuronal Responses After Nerve Root Compression Injury
Stapp car crash journal, 2011Co-Authors: Kristen J Nicholson, Julia C. Quindlen, Beth A WinkelsteinAbstract:Cervical Nerve Roots are susceptible to Compression injuries of various durations. The duration of an applied Compression has been shown to contribute to both the onset of persistent pain and also the degree of spinal cellular and molecular responses related to nociception. This study investigated the relationship between peripherally-evoked activity in spinal cord neurons during a Root Compression and the resulting development of axonal damage. Electrically-evoked spikes were measured in the spinal cord as a function of time during and after (post-Compression) a 15 minute Compression of the C7 Nerve Root. Compression to the Root significantly (p=0.035) reduced the number of spikes that were evoked over time relative to sham. The critical time for Compression to maximally reduce evoked spikes was 6.6±3.0 minutes. A second study measured the post- Compression evoked neuronal activity following Compression applied for a shorter, sub-threshold time (three minutes). Ten minutes after Compression was removed, the discharge rate remained significantly (p=0.018) less than baseline by 58±25% relative to sham after the 15 minute Compression, but returned to within 3±33% of baseline after the three minute Compression. Axonal damage was evident in the Nerve Root at day seven after Nerve Root Compression only after a 15 minute Compression. These studies demonstrate that even a transient mechanical insult to the Nerve Root is sufficient to induce sustained neuronal dysfunction and axonal pathology associated with pain, and results provide support that such minor neural tissue traumas can actually induce long-lasting functional deficits.
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The Duration of a Nerve Root Compression Modulates Evoked Neuronal Responses in a Rat Model of Painful Injury
ASME 2011 Summer Bioengineering Conference Parts A and B, 2011Co-Authors: Kristen J Nicholson, Beth A WinkelsteinAbstract:The annual incidence for neck pain in the adult population is 30–50% [1]. The cervical Nerve Roots are at risk for mechanical injury due to impingement of surrounding structures which can result in pain and numbness [2]. During Nerve Root Compression, an immediate, brief increase in spontaneous afferent activity and a gradual decrease in electrically evoked axonal conduction have been reported [3,4]. Although previous studies demonstrate that a transient cervical Nerve Root Compression induces persistent behavioral sensitivity [5,6], it is not known how the tissue mechanics during loading modulate neuronal function or how they relate to the onset of pain. Therefore, the goal of this study was to quantify neuronal activity in the spinal cord as a function of the duration of applied Compression by measuring both electrically-evoked and spontaneous afferent activity during a transient Compression of the cervical Nerve Root in a rat model of pain [5,6].Copyright © 2011 by ASME
Mark A Pinnington - One of the best experts on this subject based on the ideXlab platform.
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reliability and diagnostic validity of the slump knee bend neurodynamic test for upper mid lumbar Nerve Root Compression a pilot study
Physiotherapy, 2011Co-Authors: Kate Trainor, Mark A PinningtonAbstract:Abstract Objectives It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar Nerve Root Compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar Nerve Root Compression in subjects with suspected lumbosacral radicular pain. Design Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Setting Orthopaedic spinal clinic, secondary care. Participants Sixteen patients with radicular leg pain. Results All four subjects with mid lumbar Nerve Root Compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Conclusions Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar Nerve Root Compression. Further investigation is needed on larger numbers of patients to confirm these findings.
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Reliability and Diagnostic Validity of the Slump Knee Bend Neurodynamic Test for Upper/Mid Lumbar Nerve Root Compression: A Pilot Study
Physiotherapy, 2010Co-Authors: Kate Trainor, Mark A PinningtonAbstract:Abstract Objectives It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar Nerve Root Compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar Nerve Root Compression in subjects with suspected lumbosacral radicular pain. Design Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Setting Orthopaedic spinal clinic, secondary care. Participants Sixteen patients with radicular leg pain. Results All four subjects with mid lumbar Nerve Root Compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Conclusions Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar Nerve Root Compression. Further investigation is needed on larger numbers of patients to confirm these findings.
Kate Trainor - One of the best experts on this subject based on the ideXlab platform.
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reliability and diagnostic validity of the slump knee bend neurodynamic test for upper mid lumbar Nerve Root Compression a pilot study
Physiotherapy, 2011Co-Authors: Kate Trainor, Mark A PinningtonAbstract:Abstract Objectives It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar Nerve Root Compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar Nerve Root Compression in subjects with suspected lumbosacral radicular pain. Design Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Setting Orthopaedic spinal clinic, secondary care. Participants Sixteen patients with radicular leg pain. Results All four subjects with mid lumbar Nerve Root Compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Conclusions Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar Nerve Root Compression. Further investigation is needed on larger numbers of patients to confirm these findings.
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Reliability and Diagnostic Validity of the Slump Knee Bend Neurodynamic Test for Upper/Mid Lumbar Nerve Root Compression: A Pilot Study
Physiotherapy, 2010Co-Authors: Kate Trainor, Mark A PinningtonAbstract:Abstract Objectives It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar Nerve Root Compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar Nerve Root Compression in subjects with suspected lumbosacral radicular pain. Design Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Setting Orthopaedic spinal clinic, secondary care. Participants Sixteen patients with radicular leg pain. Results All four subjects with mid lumbar Nerve Root Compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Conclusions Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar Nerve Root Compression. Further investigation is needed on larger numbers of patients to confirm these findings.
Raymond D Hubbard - One of the best experts on this subject based on the ideXlab platform.
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transient cervical Nerve Root Compression modulates pain load thresholds for allodynia and sustained changes in spinal neuropeptide expression
Journal of Biomechanics, 2008Co-Authors: Raymond D Hubbard, Zhen Chen, Beth A WinkelsteinAbstract: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.
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transient cervical Nerve Root Compression in the rat induces bilateral forepaw allodynia and spinal glial activation mechanical factors in painful neck injuries
Spine, 2005Co-Authors: Raymond D Hubbard, Beth A WinkelsteinAbstract: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.