Transient cervical nerve root compression modulates pain:​ load thresholds for allodynia and sustained changes in spinal neuropeptide expression

Hubbard, Raymond D.<sup>1</sup>; Chen, Zhen<sup>2</sup>; Winkelstein, Beth A.<sup>1</sup>

Affiliations

¹Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104-6321, USA

²Department of Biostatistics, University of Pennsylvania, Philadelphia, PA 19104, USA

Abstract and keywords

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 (0–110 mN) 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 (26.29 mN), while thresholds for allodynia on day 7 were similar for the ipsilateral (38.16 mN) and contralateral forepaw (38.26 mN). CGRP, but not SP, significantly decreased with load; the thresholds for ipsilateral and contralateral CGRP decreases corresponded to 19.52 and 24.03 mN, respectively. These thresholds suggest bilateral allodynia may be mediated by spinal mechanisms, and that these mechanisms depend on the magnitude of load.

Keywords: Nerve root; Cervical; Load; Neck pain; Threshold

Links

DOI: 10.1016/j.jbiomech.2007.09.026

PubMed: 17976629

WoS: 000253873000024

History

Accepted: 2007-09-25

Cited Works (8)

Year	Entry
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2005	Hubbard RD, Winkelstein BA. Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine. September 1, 2005;30(17):1924-1932.
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Cited By (14)

Year	Entry
2015	Crosby ND, Smith JR, Winkelstein BA. Pain biomechanics. In: Yoganandan N, Nahum AM, Melvin JW, eds. Accidental Injury: Biomechanics and Prevention. 3rd ed. New York: Springer; 2015:549-580.
2008	Hubbard RD, Quinn KP, Martinez JJ, Winkelstein BA. The role of graded nerve root compression on axonal damage, neuropeptide changes, and pain-related behaviors. Stapp Car Crash J. 2008;52:33-58. SAE 2008-22-0002.
2011	Nicholson KJ, Quindlen JC, Winkelstein BA. Development of a duration threshold for modulating evoked neuronal responses after nerve root compression injury. Stapp Car Crash J. 2011;55:1-24.
2013	Zhang S, Nicholson KJ, Smith JR, Gilliland TM, Syré PP, Winkelstein BA. The roles of mechanical compression and chemical irritation in regulating spinal neuronal signaling in painful cervical nerve root injury. Stapp Car Crash J. November 2013;57:219-242.
2009	Siegmund GP, Winkelstein BA, Ivancic PC, Svensson MY, Vasavada A. The anatomy and biomechanics of acute and chronic whiplash injury. Traffic Inj Prev. 2009;10(2):101-112.
2008	Hubbard RD. An in Vivo Model of Transient Cervical Nerve Root Compression: Thresholds for Mechanical Allodynia and Neuronal Responses [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2008.
2009	Rothman SM. Cell-Specific Inflammatory Spinal Responses in Cervical Nerve Root Compression: Cellular Reactivity and Cytokines in Pain [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2009.
2013	Nicholson K. Defining the Role of Mechanical Signals During Nerve Root Compression in the Development of Sustained Pain and Neurophysiological Correlates That Develop in the Injured Tissue and Spinal Cord [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2013.
2014	Crosby ND. Development of Spinal Neuronal Hyperexcitability and Structural Plasticity After Cervical Facet Injury: Implications for Modulating Persistent Pain [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2014.
2015	Smith JR. Defining the Role of Blood-Spinal Cord Barrier Breakdown and Spinal Thrombin Signaling in the Development of Pain Following Neural Trauma [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2015.
2008	Drake JDM. Axial Twist Loading of the Spine: Modulators of Injury Mechanisms and the Potential for Pain Generation [PhD thesis]. University of Waterloo; 2008.
2014	Gallagher KM. The Relationships of Prolonged Standing Induced Low Back Pain Development With Lumbopelvic Posture and Movement Patterns [PhD thesis]. University of Waterloo; 2014.
2014	Gooyers CE. Exploring Interactions Between Force, Repetition and Posture on Low Back Joint Loading and Intervertebral Disc Injury [PhD thesis]. University of Waterloo; 2014.
2017	McKinnon CD. Axial Twist of the Lumbar Spine: Mechanical Responses to Twisted Postures and Potential Factors for Workplace Injury [PhD thesis]. University of Waterloo; 2017.