Mechanical Thresholds for Initiation and Persistence of Pain Following Nerve Root Injury: Mechanical and Chemical Contributions at Injury

[+] Author and Article Information
Beth A. Winkelstein

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104

Joyce A. DeLeo

Departments of Anesthesiology & Pharmacology & Toxicology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756

J Biomech Eng 126(2), 258-263 (May 04, 2004) (6 pages) doi:10.1115/1.1695571 History: Received June 14, 2002; Revised December 01, 2003; Online May 04, 2004
Copyright © 2004 by ASME
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Deyo,  R. A., and Tsui-Wu,  Y. J., 1987, “Descriptive Epidemiology of Low-Back Pain and its Related Medical Care in the United States,” Spine, 12, pp. 264–268.
Frymoyer,  J., and Cats-Baril,  W., 1991, “An Overview of the Incidences and Costs of Low Back Pain,” Orthop. Clin. North Am., 22, pp. 263–271.
Frymoyer, J., and Durett, C., 1999, “The Economics of Spinal Disorders,” The Adult Spine: Principles and Practice, Frymoyer, J. W., ed., Lippincott-Raven Publishers, Philadelphia.
Hollingworth,  W., Dixon,  A. K., Todd,  C. J., Bell,  M. I., Antoun,  N. M., Arafat,  Q., Girling,  S., Karia,  K. R., and Laing,  R. J., 1998, “Self Reported Health Status and Magnetic Resonance Imaging Findings in Patients with Low Back Pain,” Eur. Spine J., 7, pp. 369–375.
Olmarker,  K., and Myers,  R. R., 1998, “Pathogenesis of Sciatic Pain: Role of Herniated Nucleus Pulposus and Deformation of Spinal Nerve Root and Dorsal Root Ganglion,” Pain, 78, pp. 99–105.
Rydevik, B., Hasue, M., and Wehling, P., 1996, “Etiology of Sciatic Pain and Mechanisms of Nerve Root Compression,” The Lumbar Spine, Wiesel, S. W., Weinstein, J. N., Herkowitz, H., Dvorak, J., Bell, G., eds., WB Saunders Co., Philadelphia, pp. 123–141.
Vucetic,  N., Astrand,  P., Guntner,  P., and Svensson,  O., 1999, “Diagnosis and Prognosis in Lumbar Disc Herniation,” Clin. Orthop., 361, pp. 116–122.
Wall, P., and Melzack, R., 1994, Textbook of Pain, 3rd Edition, London: Churchill Livingstone.
Weinstein, J., and Gordon, S., 1996, Low Back Pain: A Scientific and Clinical Overview, Illinois: AAOS.
DeLeo,  J. A., and Winkelstein,  B. A., 2002, “Physiology of Chronic Spinal Pain Syndromes: From Animal Models to Biomechanics,” Spine, 27, pp. 2526–2537.
Hashizume,  H., DeLeo,  J. A., Colburn,  R. W., and Weinstein,  J. N., 2000, “Spinal Glial Activation and Cytokine Expression after Lumbar Root Injury in the Rat,” Spine, 25, pp. 1206–1217.
Howe,  J., Loesser,  J., and Calvin,  W., 1977, “Mechanosensitivity of Dorsal Root Ganglia and Chronically Injured Axons: A Physiological Basis for the Radicular Pain of Nerve Root Compression,” Pain, 3, pp. 25–41.
Kawakami,  M., Weinstein,  J. N., Chatani,  K., Spratt,  K. F., Meller,  S. T., and Gebhardt,  G. F., 1994, “Experimental Lumbar Radiculopathy. Behavioral and Histologic Changes in a Model of Radicular Pain after Spinal Nerve Root Irritation with Chromic Gut Ligatures in the Rat,” Spine, 19, pp. 1795–1802.
Winkelstein,  B. A., Rutkowski,  M. D., Weinstein,  J. N., and DeLeo,  J. A., 2001, “Quantification of Neural Tissue Injury in a Rat Radiculopathy Model: Comparison of Local Deformation, Behavioral Outcomes, and Spinal Cytokine mRNA for Two Surgeons,” J. Neurosci. Methods, 111, pp. 49–57.
Winkelstein,  B. A., Weinstein,  J. N., and DeLeo,  J. A., 2002, “The Role of Mechanical Deformation in Lumbar Radiculopathy: An in vivo Model,” Spine, 27, pp. 27–33.
Hunt, J., Fraser, R., Weinstein, J., and DeLeo, J., 2000, “A new model of lumbar radiculopathy: validation of the use of the chromic gut model to study the pathophysiology of radicular pain,” Proceedings of the International Society for the Study of the Lumbar Spine Annual Conference, Adelaide, Australia, Abstract #43.
Colburn,  R., Rickman,  A., and DeLeo,  J., 1999, “The Effect of Site and Type of Nerve Injury on Spinal Glial Activation and Neuropathic Pain Behavior,” Exp. Neurol., 157, pp. 289–304.
Pedowitz,  R., Garfin,  S., Massie,  J., Hargens,  A., Swenson,  M., Myers,  R., and Rydevik,  B., 1992, “Effects of Magnitude and Duration of Compression on Spinal Nerve Root Conduction,” Spine, 17, pp. 194–199.
Fung, Y. C., 1965, Foundations of Solid Mechanics, Prentice-Hall, Inc.: Englewood Cliffs, NJ.
DeLeo, J. A., and Colburn, R. W., 1996, “The Role of Cytokines in Nociception and Chronic Pain,” Low Back Pain: A Scientific and Clinical Overview, Weinstein, J. N., Gordon, S. L. eds., AAOS Publishers, Rosemont, IL, pp. 163–185.
Bain,  A. C., Raghupathi,  R., and Meaney,  D. F., 2001, “Dynamic Stretch Correlates to Both Morphological Abnormalities and Electrophysiological Impairment in a Model of Traumatic Axonal Injury,” J. Neurotrauma, 18, pp. 499–511.
Olmarker,  K., Rydevik,  B., and Nordborg,  C., 1993, “Autologous Nucleus Pulposus Induces Neurophysiologic and Histologic Changes in Porcine Cauda Equina Nerve Roots,” Spine, 18, pp. 1425–1432.
Ozaktay,  A. C., Cavanaugh,  J. M., Asik,  I., DeLeo,  J. A., and Weinstein,  J. N., 2002, “Dorsal Root Sensitivity to Interleukin-1 Beta, Interleukin-6 and Tumor Necrosis Factor in Rats,” Eur. Spine J., 11, pp. 267–475.
Winkelstein,  B. A., and DeLeo,  J. A., 2002, “Nerve Root Tissue Injury Severity Differentially Modulates Spinal Glial Activation in a Rat Lumbar Radiculopathy Model: Considerations for Persistent Pain,” Brain Res., 956, pp. 294–301.
Winkelstein, B. A., Finsness, E. D., Ridgway, A. B., and DeLeo, J. A., 2002, “Anatomic and Biomechanical Considerations for Painful Lumbar Radiculopathy Models.” Society for Neuroscience 32nd Annual Meeting, #758.7.
Inufusa,  A., An,  H. S., Lim,  T., Hasegawa,  T., Haughton,  V. M., and Nowicki,  B. H., 1996, “Anatomic Changes of the Spinal Canal and Intervertebral Foramen Associated with Flexion-Extension Movement,” Spine, 21, pp. 2412–2420.
Fujiwara,  A., An,  H. S., Lim,  T., and Haughton,  V. M., 2001, “Morphologic Changes in the Lumbar Intervertebral Foramen Due to Flexion-Extension, Lateral Bending, and Axial Rotation,” Spine, 26, pp. 876–882.
Schmid,  M. R., Stucki,  G., Duewell,  S., Wildermuth,  S., Romanowski,  B., and Hodler,  J., 1999, “Changes in Cross-Sectional Measurements of the Spinal Canal and Intervertebral Foramina as a Function of Body Position,” Americal Journal of Radiology, 172, pp. 1095–1102.
DeLeo,  J. A., and Yezierski,  R. P., 2001, “The Role of Neuroinflammation and Neuroimmune Activation in Persistent Pain,” Pain, 90, pp. 1–6.
Winkelstein,  B. A., Rutkowski,  M. D., Sweitzer,  S. M., Pahl,  J. L., and DeLeo,  J. A., 2001, “Nerve Injury Proximal or Distal to the DRG Induces Similar Spinal Glial Activation and Selective Cytokine Expression but Differential Behavioral Responses to Pharmacological Treatment,” J. Comp. Neurol., 438, pp. 127–139.
Maves,  T. J., Pechman,  P. S., Gebhart,  G. F., and Meller,  S. T., 1993, “Possible Chemical Contribution from Chromic Gut Sutures Produces Disorders of Pain Sensation Like Those Seen in Man,” Pain, 54, pp. 57–69.


Grahic Jump Location
The upper set of in vivo images on the left shows the initial unligated (reference) configuration (left) and the nerve root immediately following ligation (right). Superimposed on each image are the set of digitized boundary points along the nerve root (white dots) and the bony positional markers (black dots). The corresponding curve fits for the digitized nerve root boundaries are also shown in the set of images below them. The schematic on the right illustrates the geometric definitions for calculating radial strains along the nerve root. The radial strain magnitudes reported in this work were calculated in the region of maximal compression, indicated in this figure by the “ligation” region.
Grahic Jump Location
Mean mechanical sensitivity for all injury groups (low, tight, chromic, sham, and chromic exposure) of animals. Foot lift response frequency to stimulation with 12 gm von Frey filament is depicted over the 14 days of the study. There was a significant (p<0.0005) increase in mean mechanical allodynia for the tight and chromic ligation animals compared to both sham groups and the low silk ligation animals. Of note is the finding that while the allodynia of the tight and chromic animals were not significantly different, the applied nerve root strain in the tight group was significantly higher (p=0.001) than that applied in the chromic ligation animals. The total number of responses resulting from 30 stimulations per animal was recorded and the group average and standard error are reported here. Behavioral responses for 2 gm von Frey filament testing were similar and are not shown here.
Grahic Jump Location
The overall mechanical sensitivity shows no significant correlation with the applied ligation strain in the presence of inflammatory chromic gut material. Overall mechanical sensitivity is measured by total number of paw withdrawals when tested using a 12 gram von Frey filament. The correlation coefficient (r) of this relationship is 0.151.
Grahic Jump Location
In contrast to the chromic ligations, overall mechanical sensitivity is significantly correlated with the applied ligation strain in the absence of inflammatory material. Overall mechanical sensitivity is measured by total number of paw withdrawals when tested using a 12 gram von Frey filament. The correlation coefficient (r) of this relationship is 0.776 and is significant at p<0.05.
Grahic Jump Location
This plot demonstrates the logistic regression analysis of mechanical tissue strains required to produce persistent pain in this ligation model. Each ligation injury was given a pain score of 1 or 0 based on the existence (1) or absence (0) of persistent mechanical allodynia over 14 days. Scores were potted versus the applied ligation strain. This analysis predicted the 50th percentile strain of 20.8% applied strain and the 95th percentile threshold for pain persistence at a strain of 22.2%. These thresholds are indicated by dotted and straight lines on this plot. Individual animal responses are shown as squares. Thresholds for pain initiation were determined using similar approaches (not shown).




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