Demonstration of substance p, calcitonin gene-related peptide, and protein gene product 9.5 containing nerve fibers in human cervical facet joint capsules

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Kallakuri, Srinivasu¹; Singh, Anita¹; Chen, Chaoyang¹; Cavanaugh, John M.¹

Demonstration of substance p, calcitonin gene-related peptide, and protein gene product 9.5 containing nerve fibers in human cervical facet joint capsules

Spine. June 1, 2004;29(11):1182-1186

©2004 Lippincott Williams & Wilkins, Inc.

Affiliations

¹Bioengineering Center, Wayne State University, Detroit, MI
Abstract and keywords

Study Design: Human cervical facet joint capsules were evaluated by immunohistochemistry.

Objectives: To study the neuropeptide innervation of the cadaveric cervical facet joint capsules.

Summary of Background Data: Various clinical and biomechanical studies indicate a role for cervical facet joint capsules in the etiology of neck pain. However, studies on innervation of these capsules are very limited. There is also a dearth of studies on the neuropeptide nature of this innervation.

Methods: Facet joint capsules harvested from unembalmed cadavers were studied by the avidin biotin peroxidase method for the presence of nerve fibers. Neuropeptide innervation was investigated by using antisera to substance P and calcitonin gene-related peptide. Antisera to protein gene product 9.5 (PGP 9.5), a general neuronal marker, were also used.

Results: In a study of 12 human cervical facet joint capsules, short segments of substance P were observed in 6 capsules, while fibers reactive to calcitonin generelated peptide were demonstrated in 7 capsules. Nerve fibers immunoreactive to protein gene product 9.5 were also observed in 9 of the 14 capsules studied. Protein gene product 9.5 reactive fibers were the most extensively distributed fibers, observed as bundles and also as single fibers.

Conclusions: An abundance of protein gene product 9.5 reactive nerve fibers indicates an extensive innervation of the cervical facet joint capsules. The presence of substance P and calcitonin gene-related peptide reactive nerve fibers in a population of these lends credence to cervical facet joint capsules as a key source of neck pain.

Keywords: cervical facet joint capsule; whiplash; nerve innervation; substance P; calcitonin gene-related peptide
Links

DOI: 10.1097/00007632-200406010-00005

PubMed: 15167655

WoS: 000221812800004

Ovid: 00007632-200406010-00005
History

Received: 2003-05-05

Revised: 2003-06-24

Accepted: 2003-08-06

Cited Works (12)

Year	Entry
1998	Yoganandan N, Pintar FA, Kumaresan S, Elhagediab A. Biomechanical assessment of human cervical spine ligaments. In: Proceedings of the 42nd Stapp Car Crash Conference. November 2-4, 1998; Tempa, AZ. Warrendale, PA: Society of Automotive Engineers:223-236. SAE 983159.
1995	Barnsley L, Lord SM, Wallis BJ, Bogduk N. The prevalence of chronic cervical zygapophysial joint pain after whiplash. Spine. January 1995;20(1):20-25.
1994	Barnsley L, Lord S, Bogduk N. Whiplash injury. Pain. September 1994;58(3):283-307.
2000	Deng B, Begeman PC, Yang KH, Tashman S, King AI. Kinematics of human cadaver cervical spine during low speed rear-end impacts. Stapp Car Crash J. 2000;44:171-188. SAE 2000-01-SC13.
1997	Ono K, Kaneoka K, Wittek A, Kajzer J. Cervical injury mechanism based on the analysis of human cervical vertebral motion and head-neck-torso kinematics during low speed rear impacts. In: Proceedings of the 41st Stapp Car Crash Conference. November 13-14, 1997; Lake Buena Vista, FL. Warrendale, PA: Society of Automotive Engineers:339-356. SAE 973340.
2000	Siegmund G, Myers BS, Davis MB, Bohnet HF, Winkelstein BA. Human cervical motion segment flexibility and facet capsular ligament strain under combined posterior shear, extension and axial compression. Stapp Car Crash J. 2000;44:159-170. SAE 2000-01-SC12.
2001	Inami S, Shiga T, Tsujino A, Yabuki T, Okado N, Ochiai N. Immunohistochemical demonstration of nerve fibers in the synovial fold of the human cervical facel joint. J Orthop Res. July 2001;19(4):593-506.
2001	Bogduk N, Yoganandan N. Biomechanics of the cervical spine, III: minor injuries. Clin Biomech (Bristol, Avon). May 2001;16(4):267-275.
1999	Winkelstein BA, Nightingale RW, Richardson WJ, Myers BS. Cervical facet joint mechanics: its application to whiplash injury. In: Proceedings of the 43rd Stapp Car Crash Conference. October 25-27, 1999; San Diego, CA. Warrendale, PA: Society of Automotive Engineers:243-252. SAE 99SC15.
1996	Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash: a placebo-controlled prevalence study. Spine. August 1996;21(15):1737-1744.
1994	McLain RF. Mechanoreceptor endings in human cervical facet joints. Spine. March 1994;19(5):495-501.
1992	Aprill C, Bogduk N. The prevalence of cervical zygapophyseal joint pain: a first approximation. Spine. July 1992;17(7):744-747.

Cited By (18)

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.
2006	Quinn KP, Winkelstein BA. Application of quantitative polarized light techniques for characterizing ligament fiber kinematics during facet joint loading. In: Proceedings of the 34th International Workshop on Human Subjects for Biomechanical Research. 2006.119-132.
2007	Stemper BD, Yoganandan N, Gennarelli TA, Pintar FA. Toward a lower neck rear impact injury criterion: correlation of lower neck loads with spinal kinematics. In: Proceedings of the 2007 International IRCOBI Conference on the Biomechanics of Impact. September 19-21, 2007; Maastricht, The Netherlands.249-260.
2004	Lee KE, Davis MB, Mejilla RM, Winkelstein BA. In vivo cervical facet capsule distraction: mechanical implications for whiplash and neck pain. Stapp Car Crash J. 2004;48:373-395. SAE 2004-22-0016.
2005	Lu Y, Chen C, Kallakuri S, Patwardhan A, Cavanaugh JM. Neural response of cervical facet joint capsule to stretch: a study of whiplash pain mechanism. Stapp Car Crash J. 2005;49:49-65. SAE 2005-22-0003.
2011	Azar NR, Kallakuri S, Chen C, Cavanaugh JM. Muscular response to physiologic tensile stretch of the caprine C5/6 facet joint capsule: dynamic recruitment thresholds and latencies. Stapp Car Crash J. 2011;55:441-460.
2007	Quinn KP, Winkelstein BA. Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain. J Biomech. 2007;40(10):2299-2306.
2011	Jaumard NV, Welch WC, Winkelstein BA. Spinal facet joint biomechanics and mechanotransduction in normal, injury and degenerative conditions. J Biomech Eng. July 2011;133(7):071010.
2005	Chen C, Lu Y, Cavanaugh JM, Kallakuri S, Patwardhan A. Recording of neural activity from goat cervical facet joint capsule using custom-designed miniature electrodes. Spine. June 15, 2005;30(12):1367-1372.
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	Lee KE. An Engineering Approach to Understanding Painful Facet -Mediated Injury: Insights on Biomechanics and Neuropeptide Responses in a Rat Model [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2008.
2010	Quinn KP. Integrating Electrophysiological, Mechanical, and Optical Methods to Define the Mechanisms of Painful Facet Joint Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.
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	Kras JV. The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2015.
2020	Shen D. Investigation of Whiplash Associated Disorders Using Finite Element Neck Models With Active Musculature in Frontal, Rear and Lateral Impact [Master's thesis]. University of Waterloo; 2020.
2016	Shaw C. Identifying Axonal Injury in Cervical Facet Joint Capsules as a Result of High-Rate Tensile Stretch in an in-Vivo Goat Model [Master's thesis]. University of Windsor; 2016.
2005	Sundararajan S. Effect of Head-Neck Position on Cervical Facet Stretch of Post Mortem Human Subjects During Low Speed Rear End Impacts [PhD thesis]. Detroit, MI: Wayne State University; 2005.
2009	Azar NO. Muscular Response to Tensile Loading of the Cervical Facet Joint Capsule: A Potential Whiplash Pain Mechanism [PhD thesis]. Detroit, MI: Wayne State University; May 2009.