Abstract
Painful injury is a tremendous problem affecting a large proportion of the population during their lifetime. Pain most commonly results from trauma and/or injury, with the spine as the most common injury site for producing chronic pain. This chapter reviews relevant anatomy, mechanics and techniques used to study cervical spine pain in particular, since it is the region most prone to injury and because the largest body of research has been in this region. In vivo, many behavioral assessments exist to functionally measure painful outcomes, with hyperalgesia and allodynia as the two primary classes of behavioral responses. Both provide quantitative measures of pain that relate to the clinical presentation of symptoms. This chapter begins with a brief review of the anatomical tissues that are most at risk for injury and pain generation. This is followed by a review highlighting the cellular and molecular mechanisms of nociception and pain, addressing modifications in the periphery and in the central nervous system (CNS). The relationship between injury biomechanics and the local and spinal cellular responses are presented in the context of nociception and pain, with specific focus on injury to the facet capsule and nerve root because of their common involvement in cervical spine injury. Lastly, a brief review of experimental methodologies used to study pain biomechanics, ranging from the macroscopic to the cellular and molecular scales, is provided along with contextualization of the relative advantages and limitations of each. A brief summary integrates all of the sections to identify future areas of research that will define a more detailed understanding of pain biomechanics.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Breivik H, Collett B, Ventafridda V et al (2006) Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 10(4):287–333
Hogg-Johnson S, van der Velde G, Carroll LJ et al (2008) The burden and determinants of neck pain in the general population. Eur Spine J 17(S1):S39–S51
Loeser JD, Treede RD (2008) The Kyoto protocol of IASP basic pain terminology. Pain 137(3):473–477
DeLeo JA, Winkelstein BA (2002) Physiology of chronic spinal pain syndromes: from animal models to biomechanics. Spine 27(22):2526–2537
Antonacci MD, Mody DR, Heggeness MH (1998) Innervation of the human vertebral body: a histologic study. J Spinal Disord 1(6):526–531
Inami S, Shiga T, Tsujino A et al (2001) Immunohistochemical demonstration of nerve fibers in the synovial fold of the human cervical facet joint. J Orthop Res 19(4):593–596
Palmgren T, Gronblad M, Virri J et al (1999) An immunohistochemical study of nerve structures in the anulus fibrosus of human normal lumbar intervertebral discs. Spine 24(20):2075–2079
Rhalmi S, Yahia LH, Newman N et al (1993) Immunohistochemical study of nerves in lumbar spine ligaments. Spine 18(2):264–267
Bland JH (1990) Anatomy and physiology of the cervical spine. Semin Arthritis Rheum 20(1):1–20
Clark CR (ed) (2005) The cervical spine. Lippincott, Philadelphia
Fagan A, Moore R, Vernon Roberts B et al (2003) ISSLS prize winner: the innervation of the intervertebral disc: a quantitative analysis. Spine 28(23):2570–2576
Watson C, Paxinos G, Kayalioglu G (eds) (2009) The spinal cord. Elsevier, London
Ozawa T, Ohtori S, Inoue G et al (2006) The degenerated lumbar intervertebral disc is innervated primarily by peptide-containing sensory nerve fibers in humans. Spine 31(21):2418–2422
Yoshizawa H, O’Brien JP, Smith WT et al (1980) The neuropathology of intervertebral discs removed for low-back pain. J Pathol 132(2):95–104
Wang DL, Jiang SD, Dai LY (2007) Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine 32(23):2521–2528
Freemont AJ (2009) The cellular pathobiology of the degenerated intervertebral disc and discogenic back pain. Rheumatology 48:5–10
Freemont AJ, Peacock TE, Goupille P et al (1997) Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 350:178–181
Ohtori S, Takahashi K, Chiba T et al (2002) Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar intervertebral discs in rats. Ann Anat 184:235–240
Branconi JL, Guarino BB, Baig HA et al (2012) Painful whole body vibration increases NGF and BDNF in cervical intervertebral discs in the rat. Paper presented at the northeast bioengineering conference, Philadelphia
Kartha S, Zeeman M, Baig H et al (2014) Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration. Spine 39(19):1542–1548
Kokubo Y, Uchida K, Kobayashi S et al (2008) Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. J Neurosurg Spine 9(3):285–295
Panjabi MM, Oxland TR, Parks EH (1991) Quantitative anatomy of cervical spine ligaments part 1: upper cervical spine. J Spinal Disord 4(3):270–276
Panjabi MM, Oxland TR, Parks EH (1991) Quantitative anatomy of cervical spine ligaments part 2: middle and lower cervical spine. J Spinal Disord 4(3):277–285
Curatolo M, Bogduk N, Ivancic PC et al (2011) The role of tissue damage in whiplash-associated disorders. Spine 36(25S):S309–S315
Siegmund GP, Winkelstein BA, Ivancic PC et al (2009) The anatomy and biomechanics of acute and chronic whiplash injury. Traffic Inj Prev 10(2):101–112
Higuchi K, Sato T (2002) Anatomical study of lumbar spine innervation. Folia Morphol (Warsz) 61(2):71–79
Imai S, Hukuda S, Maeda T (1995) Dually innervating nociceptive networks in the rat lumbar posterior longitudinal ligaments. Spine 20(19):2086–2092
el-Bohy A, Cavanaugh JM, Getchell ML et al (1988) Localization of substance P and neurofilament immunoreactive fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. Brain Res 460(2):379–382
Kallakuri S, Cavanaugh JM, Blagoev DC (1998) An immunohistochemical study of innervation of lumbar spinal dura and longitudinal ligaments. Spine 23(4):403–411
Imai S, Konttinen YT, Tokunaga Y et al (1997) An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions. Spine 22(17):1941–1947
Yahia LH, Newman N, Rivard CH (1988) Neurohistology of lumbar spine ligaments. Acta Orthop Scand 59(5):508–512
Yamada H, Honda T, Yaginuma H et al (2001) Comparison of sensory and sympathetic innervation of the dura mater and posterior longitudinal ligament in the cervical spine after removal of the stellate ganglion. J Comp Neurol 434(1):86–100
Jiang H, Russell G, Raso JV et al (1995) The nature and distribution of the innervation of human supraspinal and interspinal ligaments. Spine 20(8):869–876
McLain RF (1994) Mechanoreceptor endings in human cervical facet joints. Spine 19(5):495–501
McClain RF, Raiszadeh KR (1995) Mechanoreceptor endings of the cervical, thoracic, and lumbar spine. Iowa Orthop J 15:147–155
Bogduk N, Marsland A (1988) The cervical zygapophysial joints as a source of neck pain. Spine 13(6):610–617
Kallakuri S, Singh A, Chen C et al (2004) Demonstration of substance P, calcitonin gene-related peptide, and protein gene product 9.5 containing nerve fibers in human cervical facet joint capsules. Spine 29(11):1182–1186
Dwyer A, Aprill C, Bogduk N (1990) Cervical zygapophyseal joint pain patterns. 1: A study in normal volunteers. Spine 15(6):453–457
Fukui S, Ohseto K, Shiotani M et al (1996) Referred pain distribution of the cervical zygapophyseal joints and cervical dorsal rami. Pain 68(1):79–83
Lord SM, Barnsley L, Bogduk N (1995) Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophysial joint pain: a caution. Neurosurgery 36(4):732–739
Lord SM, Barnsley L, Wallis BJ et al (1996) Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med 335(23):1721–1726
Slipman CW, Lipetz JS, Plastaras CT et al (2001) Therapeutic zygapophyseal joint injections for headaches emanating from the C2-3 joint. Am J Phys Med Rehabil 80(3):182–188
Yoganandan N, Knowles SA, Maiman DJ et al (2003) Anatomic study of the morphology of human cervical facet joint. Spine 28(20):2317–2323
Yoganandan N, Pintar FA, Cusick JF et al (1998) Head-neck biomechanics in simulated rear impact. Annu Proc Assoc Adv Automot Med 42:209–231
Webb AL, Collins P, Rassoulian H et al (2011) Synovial folds – a pain in the neck? Man Ther 16(2):118–124
Adams MA, Dolan P (2005) Spine biomechanics. J Biomech 38(10):1972–1983
Cusick JF, Yoganandan N (2012) Biomechanics of the cervical spine 4: major injuries. Clin Biomech 17(1):1–20
Myers BS, Winkelstein BA (1995) Epidemiology, classification, mechanism, and tolerance of human cervical spine injuries. Crit Rev Biomed Eng 23(5–6):307–409
Wen N, Lavaste F, Santin JJ, Lassau JP (1993) Three-dimensional biomechanical properties of the human cervical spine in vitro. I. Analysis of normal motion. Eur Spine J 2(1):2–11
White AA, Panjabi MM (1990) Clinical biomechanics of the spine, 2nd edn. Lippincott, New York
Myklebust JB, Pintar FA, Yoganandan N et al (1988) Tensile strength of spinal ligaments. Spine 13(5):526–531
Yoganandan N, Pintar F, Butler J et al (1989) Dynamic response of human cervical spine ligaments. Spine 14(10):1102–1110
Winkelstein BA (2004) Mechanisms of central sensitization, neuroimmunology & injury biomechanics in persistent pain: implications for musculoskeletal disorders. J Electromyogr Kinesiol 14(1):87–93
Winkelstein BA (2011) How can animal models inform on the transition to chronic symptoms in whiplash? Spine 36(25s):S218–S225
Fricke B, Andres KH, Von During M (2001) Nerve fibers innervating the cranial and spinal meninges: morphology of nerve fiber terminals and their structural integration. Microsc Res Techn 53(2):96–105
Kumar R, Berger RJ, Dunsker SB et al (1996) Innervation of the spinal dura – myth or reality? Spine 21(1):18–25
Yamada H, Honda T, Kikuchi S et al (1998) Direct innervation of sensory fibers from the dorsal root ganglion of the cervical dura mater of rats. Spine 23(14):1524–1529
Wieseler-Frank J, Jekich BM, Mahoney JH et al (2007) A novel immune-to-CNS communication pathway: cells of the meninges surrounding the spinal cord CSF space produce proinflammatory cytokines in response to an inflammatory stimulus. Brain Behav Immun 21(5):711–718
McMahon S, Koltzenburg M (eds) (2005) Wall and Melzack’s textbook of pain. Churchill Livingstone, London
Rexed B (1952) The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 96:415–496
Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244–256
Belanger M, Drew T, Provencher J et al (1996) A comparison of treadmill locomotion in adult cats before and after spinal transection. J Neurophysiol 76:471–491
Bresnahan JC, Beattie MS, Todd FD et al (1987) A behavioral and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device. Exp Neurol 95:548–570
Muir GD, Whishaw IQ (2000) Red nucleus lesions impair overground locomotion in rats: a kinetic analysis. Eur J Neurosci 12:1113–1122
Profyris C, Cheema SS, Zang D et al (2004) Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 15:415–436
Hausmann ON (2003) Post-traumatic inflammation following spinal cord injury. Spinal Cord 41:369–378
Sroga JM, Jones TB, Kigerl KA et al (2003) Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 462:223–240
Beric A (1997) Post-spinal cord injury pain states. Anesthesiol Clin North Am 17(2):445–463
Siddall PJ, McClelland JM, Rutkowski SB et al (2003) A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain 103:249–257
Coggeshall RE (1979) Afferent fibers in the ventral root. Neurosurgery 4(5):443–448
Hanai F, Matsui N, Hongo N (1996) Changes in responses of wide dynamic range neurons in the spinal dorsal horn after dorsal root or dorsal root ganglion compression. Spine 21(12):1408–1415
Hu SJ, Xing JL (1998) An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 77(1):15–23
Van Zundert J, Harney D, Joosten EA et al (2006) The role of the dorsal root ganglion in cervical radicular pain: diagnosis, pathophysiology, and rationale for treatment. Reg Anesth Pain Med 31(2):152–167
Kitagawa T, Fujiwara A, Kobayashi N et al (2004) Morphologic changes in the cervical neural foramen due to flexion and extension – in vivo imaging study. Spine 29(24):2821–2825
Tominaga Y, Maak TG, Ivancic PC et al (2006) Head-turned rear impact causing dynamic cervical intervertebral foramen narrowing: implications for ganglion and nerve root injury. J Neurosurg Spine 4(5):380–387
Rothman SM, Nicholson KJ, Winkelstein BA (2010) Time-dependent mechanics and measures of glial activation and behavioral sensitivity in a rodent model of radiculopathy. J Neurotrauma 27(5):803–814
Winkelstein BA, DeLeo JA (2004) Mechanical thresholds for initiation and persistence of pain following nerve root injury: mechanical and chemical contributions at injury. J Biomech Eng 126(2):258–263
Cavanaugh JM (1995) Neural mechanisms of lumbar pain. Spine 20(16):1804–1809
Mense S, Meyer H (1985) Different types of slowly conducting afferent units in cat skeletal muscle and tendon. J Physiol 363:403–417
Vasavada AN, Brault JR, Siegmund GP (2007) Musculotendon and fascicle strains in anterior and posterior neck muscles during whiplash injury. Spine 32(7):756–765
Elliott J, Jull GM, Noteboom JT (2006) Fatty infiltration in the cervical extensor muscles in persistent whiplash-associated disorders: a magnetic resonance imaging analysis. Spine 31(22):E847–E855
Elliott J, Pedler A, Kenardy J et al (2011) The temporal development of fatty infiltrates in the neck muscles following whiplash injury: an association with pain and posttraumatic stress. PLoS One 6(6):e21194
O’leary S, Falla D, Elliot JM et al (2009) Muscle dysfunction in cervical spine pain: implications for assessment and management. J Orthop Sports Phys Ther 39(5):324–333
Graven-Nielsen T, Mense S (2001) The peripheral apparatus of muscle pain: evidence from animal and human studies. Clin J Pain 17(1):2–10
Smith LL (1991) Acute-inflammation – the underlying mechanism in delayed onset muscle soreness. Med Sci Sports Exerc 23(5):542–551
Stauber WT (2004) Factors involved in strain-induced injury in skeletal muscles and outcomes of prolonged exposures. J Electromyogr Kinesiol 14(1):61–70
Winkelstein BA, McLendon RE, Barbir A et al (2001) An anatomical investigation of the human cervical facet capsule, quantifying muscle insertion area. J Anat 198(Pt 4):455–461
Siegmund GP, Sanderson DJ, Myers BS et al (2003) Rapid neck muscle adaptation alters the head kinematics of aware and unaware subjects undergoing multiple whiplash-like perturbations. J Biomech 36(4):473–482
Chopard RP, de Miranda Neto MH, Lucas GA et al (1992) The vertebral artery: its relationship with adjoining tissues in its course intra and inter transverse processes in man. Rev Paul Med 110(6):245–250
Thiel HW (1991) Gross morphology and pathoanatomy of the vertebral arteries. J Manipulative Physiol Ther 14(2):133–141
Carlson EJ, Tominaga Y, Ivancic PC et al (2007) Dynamic vertebral artery elongation during frontal and side impacts. Spine J 7(2):222–228
Chung YS, Han DH (2002) Vertebrobasilar dissection: a possible role of whiplash injury in its pathogenesis. Neurol Res 24(2):129–138
Kawchuk GN, Wynd S, Anderson T (2004) Defining the effect of cervical manipulation on vertebral artery integrity: establishment of an animal model. J Manipulative Physiol Ther 27(9):539–546
Saeed AB, Shuaib A, Al-Sulaiti G et al (2000) Vertebral artery dissection: warning symptoms, clinical features and prognosis in 26 patients. Can J Neurol Sci 27(4):292–296
Svensson MY, Aldman B, Bostrom O et al (1998) Transient pressure gradients in the pig spinal canal during experimental whiplash motion causing membrane dysfunction in spinal ganglion nerve cells. Orthopade 27(12):820–826
Steeds CE (2009) The anatomy and physiology of pain. Surgery 27(12):507–511
Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765–1768
Woolf CJ (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152:S2–S15
Coderre TJ, Katz J, Vaccarino AL et al (1993) Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 52:259–285
Dubner R, Ruda MA (1992) Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurosci 15(3):96–103
Markenson JA (1996) Mechanisms of chronic pain. Am J Med 101(1A):6S–18S
Millan MJ (1999) The induction of pain: an integrative review. Prog Neurobiol 57(1):1–164
Costigan M, Scholz J, Woolf CJ (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32
Braz JM, Nassar MA, Wood JN et al (2005) Parallel “pain” pathways arise from subpopulations of primary afferent nociceptor. Neuron 47(6):787–793
Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413(6852):203–210
Boucher TJ, McMahon SB (2001) Neurotrophic factors and neuropathic pain. Curr Opin Pharmacol 1(1):66–72
Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926
Hucho T, Levine JD (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55(3):365–376
Verri WA Jr, Cunha TM, Parada CA et al (2006) Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development? Pharmacol Ther 112(1):116–138
Ji RR, Kohno T, Moore KA et al (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26(12):696–705
Devor M (2009) Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res 196:115–128
Djouhri L, Lawson SN (2004) Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res Rev 46(2):131–145
Kohama I, Ishikawa K, Kocsis JD (2000) Synaptic reorganization in the substantia gelatinosa after peripheral nerve neuroma formation: aberrant innervation of lamina II neurons by Abeta afferents. J Neurosci 20(4):1538–1549
Woolf CJ, Shortland P, Coggeshall RE (1992) Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355:75–78
Gould HJ 3rd, Gould TN, England JD et al (2000) A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain. Brain Res 854(1–2):19–29
Matayoshi S, Jiang N, Katafuchi T et al (2005) Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat. J Physiol 569(Pt 2):685–695
Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51(2):240–264
Pezet S, McMahon SB (2006) Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 29:507–538
DeLeo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90(1–2):1–6
Chen C, Lu Y, Kallakuri S et al (2006) Distribution of Adelta and C-fiber receptors in the cervical facet joint capsule and their response to stretch. J Bone Joint Surg 88:1807–1816
Lu Y, Chen C, Kallakuri S et al (2005) Neural response of cervical facet joint capsule to stretch: a study of whiplash pain mechanism. Stapp Car Crash J 49:49–65
Crosby ND, Weisshaar CL, Winkelstein BA (2013) Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury. Neurosci Lett 542:102–106
Quinn KP, Dong L, Golder FJ et al (2010) Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. Pain 151:414–421
Lee KE, Winkelstein BA (2009) Joint distraction magnitude is associated with different behavioral outcomes and substance P levels for cervical facet joint loading in the rat. J Pain 10(4):436–445
Winkelstein BA, Santos DG (2009) An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension. Spine 33(8):856–862
Chang YW, Winkelstein BA (2011) Schwann cell proliferation and macrophage infiltration are evident at day 14 after painful cervical nerve root compression in the rat. J Neurotrauma 28(12):2429–2438
Rothman SM, Huang Z, Lee KE et al (2009) Cytokine mRNA expression in painful radiculopathy. J Pain 10(1):90–99
Rothman SM, Winkelstein BA (2010) Cytokine antagonism reduces pain and modulates spinal astrocytic reactivity after cervical nerve root compression. Ann Biomed Eng 38(8):2563–2576
Aprill C, Bogduk N (1992) The prevalence of cervical zygapophyseal joint pain: a first approximation. Spine 17(7):744–747
Barnsley L, Lord S, Bogduk N (1993) Comparative local anaesthetic blocks in the diagnosis of cervical zygapophysial joint pain. Pain 55(1):99–106
Lord SM, Barnsley L, Wallis BJ et al (1996) Chronic cervical zygapophysial joint pain after whiplash: a placebo-controlled prevalence study. Spine 21(15):1737–1744
Stemper BD, Yoganandan N, Gennarelli TA et al (2005) Localized cervical facet joint kinematics under physiological and whiplash loading. J Neurosurg Spine 3(6):471–476
Jaumard NV, Welch WC, Winkelstein BA (2011) Spinal facet joint biomechanics and mechanotransduction in normal, injury and degenerative conditions. J Biomech Eng 133(7):071010
Kaneoka K, Ono K, Inami S et al (1999) Motion analysis of cervical vertebrae during whiplash loading. Spine 24(8):763–769
Pearson AM, Ivancic PC, Ito S et al (2004) Facet joint kinematics and injury mechanisms during simulated whiplash. Spine 29(4):390–397
Bogduk N, Yoganandan N (2001) Biomechanics of the cervical spine. Part 3: minor injuries. Clin Biomech 16(4):267–275
Deng B, Begeman PC, Yang KH et al (2000) Kinematics of human cadaver cervical spine during low speed read-end impacts. Stapp Car Crash J 44:171–188
Panjabi MM (1998) Cervical spine models for biomechanical research. Spine 23:2684–2700
Panjabi MM, Cholewicki J, Nibu K et al (1998) Simulation of whiplash trauma using whole cervical spine specimens. Spine 23:17–24
Ono K, Kaneoka K, Wittek A et al (1997) Cervical injury mechanism based on the analysis of human cervical vertebral motion and head-neck-torso kinematics during low speed rear impacts. Stapp Car Crash J 41:339–356
Yoganandan N, Cusick JF, Pintar FA et al (2001) Whiplash injury determination with conventional spine imaging and cryomicrotomy. Spine 26(22):2443–2448
Sundararajan S, Prasad P, Demetropoulos CK et al (2004) Effect of head-neck position on cervical facet stretch of post mortem human subjects during low speed rear end impacts. Stapp Car Crash J 48:331–372
Winkelstein BA, Nightingale RW, Richardson WJ et al (2000) The cervical facet capsule and its role in whiplash injury: a biomechanical investigation. Spine 25(10):1238–1246
Panjabi MM, Cholewicki J, Nibu K et al (1998) Mechanism of whiplash injury. Clin Biomech 13(4):239–249
Luan F, Yang KH, Deng B et al (2000) Qualitative analysis of neck kinematics during low-speed rear-end impact. Clin Biomech 15(9):649–657
Panjabi MM, Cholewicki J, Nibu K et al (1998) Capsular ligament stretches during in vitro whiplash simulations. J Spinal Disord 11(3):227–232
Grauer JN, Panjabi MM, Cholewicki J et al (1997) Whiplash produces an S-shaped curvature of the neck with hyperextension at lower levels. Spine 22(21):2489–2494
Siegmund GP, Myers BS, Davis MB et al (2000) Human cervical motion segment flexibility and facet capsular ligament strain under combined posterior shear, extension and axial compression. Stapp Car Crash J 44:159–170
Siegmund GP, Myers BS, Davis MB et al (2001) Mechanical evidence of cervical facet capsule injury during whiplash: a cadaveric study using combined shear, compression, and extension loading. Spine 26(19):2095–2101
Yoganandan N, Pintar FA (1997) Inertial loading of the human cervical spine. J Biomech Eng 119(3):237–240
Quinn KP, Winkelstein BA (2007) Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain. J Biomech 40(10):2299–2306
Lee KE, Franklin AN, Davis MB et al (2006) Tensile cervical facet capsule ligament mechanics: failure and subfailure responses in the rodent. J Biomech 39(7):1256–1264
Chen C, Lu Y, Cavanaugh JM et al (2005) Recording of neural activity from goat cervical facet joint capsule using custom-designed miniature electrodes. Spine 30(12):1367–1372
Dong L, Winkelstein BA (2010) Simulated whiplash modulates expression of the glutamatergic system in the spinal cord suggesting spinal plasticity is associated with painful dynamic cervical facet loading. J Neurotrauma 27(1):163–174
Lee KE, Davis MB, Winkelstein BA (2008) Capsular ligament involvement in the development of mechanical hyperalgesia after facet joint loading: behavioral and inflammatory outcomes in a rodent model of pain. J Neurotrauma 25(11):1383–1393
Lee KE, Thinnes JH, Gokhin DS et al (2004) A novel rodent neck pain model of facet-mediated behavioral hypersensitivity: implications for persistent pain and whiplash injury. J Neurosci Methods 137(2):151–159
Lu Y, Chen C, Kallakuri S et al (2005) Neurophysiological and biomechanical characterization of goat cervical facet joint capsules. J Orthop Res 23:779–787
Weisshaar CL, Dong L, Bowman AS et al (2010) Metabotropic glutamate receptor-5 and protein kinase C-epsilon increase in dorsal root ganglion neurons and spinal glial activation in an adolescent rat model of painful neck injury. J Neurotrauma 27(12):2261–2271
Lu Y, Chen C, Kallakuri S et al (2005) Development of an in vivo method to investigate biomechanical and neurophysiological properties of spine facet joint capsules. Eur Spine J 14(6):565–572
Kallakuri S, Singh A, Lu Y et al (2008) Tensile stretching of cervical facet joint capsule and related axonal changes. Eur Spine J 17(4):556–563
Quinn KP, Lee KE, Ahaghotu CC et al (2007) Structural changes in the cervical facet capsular ligament: potential contributions to pain following subfailure loading. Stapp Car Crash J 51:169–187
Curatolo M, Petersen-Felix S, Arendt-Nielsen L et al (2001) Central hypersensitivity in chronic pain after whiplash injury. Clin J Pain 17(4):306–315
Herren-Gerber R, Weiss S, Arendt-Nielsen L et al (2004) Modulation of central hypersensitivity by nociceptive input in chronic pain after whiplash injury. Pain 5(4):366–376
Lee KE, Davis MB, Mejilla RM et al (2004) In vivo cervical facet capsule distraction: mechanical implications for whiplash & neck pain. Stapp Car Crash J 48:373–396
Rothman SM, Hubbard RD, Lee KE et al (2008) Detection, transmission, and perception of pain. In: Slipman C, Simeone F, Derby R (eds) Interventional spine: an algorithmic approach. Saunders, Philadelphia
Dong L, Quindlen JC, Lipschutz DE et al (2012) Whiplash-like facet joint loading initiates glutamatergic responses in the DRG and spinal cord associated with behavioral hypersensitivity. Brain Res 1461:51–63
Deriemer S, Strong J, Albert K et al (1985) Enhancement of calcium current in Aplysia neurons by phorbol ester and protein kinase C. Nature 313:313–316
Xu T, Jiang W, Du D et al (2007) Role of spinal metabotropic glutamate receptor subtype 5 in the development of tolerance to morphine-induced antinociception in rat. Neurosci Lett 420:155–159
Azkue JJ, Liu XG, Zimmermann M et al (2003) Induction of long-term potentiation of C fibre-evoked spinal field potentials requires recruitment of group I, but not group II/III metabotropic glutamate receptors. Pain 106:373–379
Derjean D, Bertrand S, Le Masson G et al (2003) Dybamic balance of metabotropic inputs causes dorsal horn neurons to switch functional states. Nat Neurosci 6:274–281
Young MR, Fleetwood-Walker SM, Dickinson T et al (1997) Behavioral and electrophysiological evidence supporting a role for group I metabotropic glutamate receptors in the mediation of nociceptive inputs to the rat spinal cord. Brain Res 777:161–169
Gwak Y, Hulsebosch C (2005) Upregulation of group I metabotropic glutamate receptors in neurons and astrocytes in the dorsal horn following spinal cord injury. Exp Neurol 195:236–243
Liang Y, Huang C, Hsu K (2005) Characterization of long-term potentiation of primary afferent transmission at trigeminal synapses of juvenile rats: essential role of subtype 5 metabotropic glutamate receptors. Pain 114:417–428
Cao H, Zhang YQ (2008) Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev 32(5):972–983
DeLeo JA, Tanga FY, Tawfik VL (2004) Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist 10(1):40–52
Suter MR, Wen YR, Decosterd I et al (2007) Do glial cells control pain? Neuron Glia Biol 3:255–268
Frymoyer JW (1998) Back pain and sciatica. N Engl J Med 318(5):291–300
Kelly JD, Aliquo D, Sitler MR et al (2000) Association of burners with cervical canal and foraminal stenosis. Am J Sports Med 28(2):214–217
Nuckley DJ, Konodi MA, Raynak GC et al (2002) Neural space integrity of the lower cervical spine: effect of normal range of motion. Spine 27(6):587–595
Abbed KM, Coumans J (2007) Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation. Neurosurgery 60(1):28–34
Caridi JM, Matthias P, Hughes AP (2011) Cervical radiculopathy: a review. HSS J 7:265–272
Harden N, Cohen M (2003) Unmet needs in the management of neuropathic pain. J Pain Symptom Manage 25(5):S12–S17
Slipman CW, Plastaras CT, Palmitier RA et al (1998) Symptom provocation of fluoroscopically guided cervical nerve root stimulation: are dynatomal maps identical to dermatomal maps? Spine 23(20):2235–2242
Ellenberg MR, Honet JC, Treanor WJ (1994) Cervical radiculopathy. Arch Phys Med Rehabil 75(3):342–532
Kawakami M, Hashizume H, Nishi H et al (2003) Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat. J Orthop Res 21(3):535–539
Rutkowski MD, Winkelstein BA, Hickey WF et al (2002) Lumbar nerve root injury induces central nervous system neuroimmune activation and neuroinflammation in the rat: relationship to painful radiculopathy. Spine 27(15):1604–1613
Sunderland S (1974) Mechanisms of cervical nerve root avulsion in injuries of the neck and shoulder. J Neurosurg 41:705–714
Krivickas LS, Wilbourn AJ (2000) Peripheral nerve injuries in athletes: a case series of over 200 injuries. Semin Neurol 20(2):225–232
Panjabi MM, Maak TG, Ivancic PC et al (2006) Dynamic intervertebral foramen narrowing during simulated rear impact. Spine 31(5):128–134
Tominaga Y, Maak TG, Ivancic PC et al (2006) Head-turned rear impact causing dynamic cervical intervertebral foramen narrowing: implications for ganglion and nerve root injury. J Neurosurg Spine 26(1):57–62
Wainner RS, Gill H (2000) Diagnosis and nonoperative management of cervical radiculopathy. J Orthop Sports Phys Ther 30(12):728–744
Singh A, Lu Y, Chaoyang C et al (2006) Mechanical properties of spinal nerve roots subjected to tension at different strain rates. J Biomech 39(9):1669–1676
Singh A, Kallakuri A, Chen C et al (2009) Structural and functional changes in nerve roots due to tension at various strains and strain rates: an in-vivo study. J Neurotrauma 26(4):627–640
Fung YC (1972) Stress-strain-history relations of soft tissues in simple elongation. In: Fung YC (ed) Biomechanics: its foundations and objectives. Prentice-Hall, Englewood Cliffs
Yoganandan N, Kumaresan S, Pintar FA (2001) Biomechanics of the cervical spine part 2. Cervical spine soft tissue responses and biomechanical modeling. Clin Biomech 16(1):1–27
Hubbard RD, Chen Z, Winkelstein BA (2008) Transient cervical nerve root compression modulates pain: load thresholds for allodynia and sustained changes in spinal neuropeptide expression. J Biomech 41:677–685
Hubbard RD, Winkelstein BA (2005) Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine 30(17):1924–1932
Winkelstein BA, DeLeo JA (2002) Nerve root injury severity differentially modulates spinal glial activation in a rat lumbar radiculopathy model: considerations for persistent pain. Brain Res 956(2):294–301
Winkelstein BA, Rutkowski MD, Weinstein JN et al (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(1):49–57
Winkelstein BA, Weinstein JN, DeLeo JA (2002) The role of mechanical deformation in lumbar radiculopathy: an in vivo model. Spine 27(1):27–33
Hubbard RD, Winkelstein BA (2008) Dorsal root compression produces myelinated axonal degeneration near the biomechanical thresholds for mechanical behavioral hypersensitivity. Exp Neurol 212(2):482–489
Nicholson KJ, Gilliland TM, Winkelstein BA (2013) Duration of nerve root compressive trauma modulates the subsequent thermal hyperalgesia & spinal expression of the glutamate transporter, GLT1. Paper presented at the Proceedings of the ASME 2013 summer bioengineering conference, Sunriver, Oregon, 26–29 Jun 2013
Nicholson KJ, Guarino BB, Winkelstein BA (2012) Transient nerve root compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGluR5 expression. Neuroscience 209:187–195
Scholz J, Woolf CJ (2007) The neuropathic triad: neurons, immune cells and glia. Nat Neurosci 10(11):1361–1368
Hubbard RD, Quinn KP, Martinez JJ et al (2008) The role of graded nerve root compression on axonal damage, neuropeptide changes, and pain-related behaviors. Stapp Car Crash J 52:33–58
Kobayashi S, Baba H, Uchida K et al (2005) Effect of mechanical compression on the lumbar nerve root: localization and changes of intraradicular inflammatory cytokines, nitric oxide, and cyclooxygenase. Spine 30(15):1699–1705
Nicholson KJ, Quindlen JC, Winkelstein BA (2011) Development of a duration threshold for modulating evoked neuronal responses after nerve root compression injury. Stapp Car Crash J 55:1–24
Olmarker K, Holm S, Rydevik B (1990) Importance of compression onset rate for the degree of impairment of impulse propagation in experimental compression injury of the porcine cauda equina. Spine 15(5):416–419
Burchiel KJ, Hsu FPK (2001) Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine 26(24):S146–S160
Finnerup NB, Jensen TS (2004) Spinal cord injury pain: mechanisms and treatment. Eur J Neurol 11(2):73–82
Hulsebosch CE, Hains BC, Crown ED et al (2009) Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev 60(1):202–213
Vierck CJ, Siddall P, Yezierski RP (2000) Pain following spinal cord injury: animal models and mechanistic studies. Pain 89(1):1–5
Yezierski RP (2009) Spinal cord injury pain: spinal and supraspinal mechanisms. J Rehabil Res Dev 46(1):95–107
Kwon BK, Tetslaff W, Grauer JN et al (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4(4):451–464
Saab CY, Waxman SG, Hains BC (2008) Alarm or curse? The pain of neuroinflammation. Brain Res Rev 58(1):226–235
Hulsebosch CE (2002) Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 26:238–255
Yamashita T, Cavanaugh JM, el-Bohy AA et al (1990) Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am 72(6):865–870
Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31(18):2151–2161
Setton LA, Chen J (2006) Mechanobiology of the intervertebral disc and relevance to disc degeneration. J Bone Joint Surg Am 88(Suppl 2):52–57
Dai LY, Jia LS (2000) Central cord injury complicating acute cervical disc herniation in trauma. Spine 25(3):331–335
Berrington NR, van Staden JF, Willers JG et al (1993) Cervical intervertebral disc prolapse associated with traumatic facet dislocations. Surg Neurol 40(5):395–399
Brault JR, Siegmund GP, Wheeler JB (2000) Cervical muscle response during whiplash: evidence of a lengthening muscle contraction. Clin Biomech 15(6):426–435
Siegmund GP, Blouin JS, Carpenter MG et al (2008) Are cervical multifidus muscles active during whiplash and startle? An initial experimental study. BMC Musculoskelet Disord 9:80
Davis SJ, Teresi LM, Bradley WG et al (1991) Cervical spine hyperextension injuries: MR findings. Radiology 180(1):245–251
Kliewer MA, Gray L, Paver J et al (1993) Acute spinal ligament disruption: MR imaging with anatomic correlation. J Magn Reson Imaging 3(6):855–861
McMahon PJ, Dheer S, Raikin SM et al (2009) MRI of injuries to the first interosseous cuneometatarsal (Lisfranc) ligament. Skeletal Radiol 38(3):255–260
Billiar KL, Sacks MS (1997) A method to quantify the fiber kinematics of planar tissues under biaxial stretch. J Biomech 30(7):753–756
Hansen KA, Weiss JA, Barton JK (2002) Recruitment of tendon crimp with applied tensile strain. J Biomech Eng 124(1):72–77
Robinson PS, Tranquillo RT (2009) Planar biaxial behavior of fibrin-based tissue-engineered heart valve leaflets. Tissue Eng Part A 15(10):2763–2772
Snedeker JG, Pelled G, Zilberman Y et al (2006) Endoscopic cellular microscopy for in vivo biomechanical assessment of tendon function. J Biomed Opt 11(6):064010
Snedeker JG, Pelled G, Zilberman Y et al (2008) An analytical model for elucidating tendon tissue structure and biomechanical function from in vivo cellular confocal microscopy images. Cells Tissues Organs 190:111–119
Tower TT, Neidert MR, Tranquillo RT (2002) Fiber alignment imaging during mechanical testing of soft tissues. Ann Biomed Eng 30(10):1221–1233
Sander EA, Barocas VH (2009) Comparison of 2D fiber network orientation measurement methods. J Biomed Mater Res A 88(2):322–331
Quinn KP, Bauman JA, Crosby ND et al (2010) Anomalous fiber realignment during tensile loading of the rat facet capsular ligament identifies mechanically induced damage and physiological dysfunction. J Biomech 43(10):1870–1875
Dickey JP, Hewlett BR, Dumas GA et al (1998) Measuring collagen fiber orientation: a two-dimensional quantitative macroscopic technique. J Biomech Eng 120(4):537–540
Tower TT, Tranquillo RT (2001) Alignment maps of tissues: I. Microscopic elliptical polarimetry. Biophys J 81(5):2954–2963
Whittaker P, Canham PB (1991) Demonstration of quantitative fabric analysis of tendon collagen using two-dimensional polarized light microscopy. Matrix 11(1):56–62
Quinn KP, Winkelstein BA (2010) Full field strain measurements of collagenous tissue by tracking fiber alignment through vector correlation. J Biomech 43(13):2637–2640
Liem LK, Simard JM, Song Y et al (1995) The patch clamp technique. Neurosurgery 36(2):382–392
Stanfa LC, Dickenson AH (2004) In vivo electrophysiology of dorsal horn neurons. In: Luo ZD (ed) Methods in molecular medicine. Humana, Totowa
Zhao Y, Inayat S, Dikin DA et al (2009) Patch clamp technique: review of the current state of the art and potential contributions from nanoengineering. Proc IMechE 222:1–11
Pine J (2006) A history of MEA development. In: Taketani M, Baudry M (eds) Advances in network electrophysiology: using multi-electrode arrays. Springer, New York
Lewicki MS (1998) A review of methods for spike sorting: the detection and classification of neural action potentials. Comput Neural Syst 9(4):R53–R78
Schouenberg J (1984) Functional and topographical properties of field potentials evoked in rat dorsal horn neurons by cutaneous C-fiber stimulation. J Physiol 356:169–192
Stett A, Egert U, Guenther E et al (2003) Biological applications of microelectrode arrays in drug discovery and basic research. Anal Bioanal Chem 377:486–495
Hains BC, Willis WD, Hulsebosch CE (2003) Temporal plasticity of dorsal horn somatosensory neurons after acute and chronic spinal cord hemisection in rat. Brain Res 970:238–241
Martindale JC, Wilson AW, Reeve AJ et al (2007) Chronic secondary hypersensitivity of dorsal horn neurons following inflammation of the knee joint. Pain 133:79–86
Vernon H, Sun K, Zhang T et al (2009) Central sensitization induced in trigeminal and upper cervical dorsal horn neurons by noxious stimulation of deep cervical paraspinal tissues in rats with minimal surgical trauma. J Manipulative Physiol Ther 32(7):506–514
Ikeda H, Heinke B, Ruscheweyh R et al (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237–1240
Randic M, Jiang MC, Cerne R (1993) Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci 13(12):5228–5241
Eytan D, Marom S (2006) Dynamics and effective topology underlying synchronization in networks of cortical neurons. J Neurosci 26(33):8465–8476
Hofmann F, Bading H (2006) Long term recordings with multi-electrode arrays: studies of transcription-dependent neuronal plasticity and axonal regeneration. J Physiol Paris 99(2–3):125–132
Kutzing MK, Luo V, Firestein BL (2011) Measurement of synchronous activity by microelectrode arrays uncovers differential effects of sublethal and lethal glutamate concentrations on cortical neurons. Ann Biomed Eng 39(8):2252–2262
Yu Z, Graudejus O, Tsay C et al (2009) Monitoring hippocampus electrical activity in vitro on an elastically deformable microelectrode array. J Neurotrauma 26:1135–1145
Cheung KC, Renaud P, Tanila H et al (2007) Flexible polyimide microelectrode array for in vivo recordings and current source density analysis. Biosens Bioelectron 22(8):1783–1790
Timko BP, Cohen-Karni T, Yu G et al (2009) Electrical recordings from hearts with flexible nanowire device arrays. Nano Lett 9(2):914–918
Viventi J, Kim DH, Moss JD et al (2010) A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology. Sci Transl Med 2(24):24ra22
Saxena T, Gilbert J, Stelzner D et al (2012) Mechanical characterization of the injured spinal cord after lateral spinal hemisection injury in the rat. J Neurotrauma 29(9):1747–1757
Levental I, Levental KR, Klein EA et al (2010) A simple indentation device for measuring micrometer-scale tissue stiffness. J Phys Condens Matter 22(19):194120
Miller WJ, Leventhal I, Scarcella D et al (2009) Mechanically induced reactive gliosis causes ATP-mediated alterations in astrocyte stiffness. J Neurotrauma 26(5):789–797
Vergara D, Martignago R, Leporatti S et al (2009) Biomechanical and proteomic analysis of IFN-β-treated astrocytes. Nanotechnology 20:244106–455115
Ouyang H, Galle B, Li J et al (2008) Biomechanics of spinal cord injury: a multimodal investigation using ex vivo guinea pig spinal cord white matter. J Neurotrauma 25(1):19–29
East E, de Oliveira DB, Golding JP et al (2010) Alignment of astrocytes increases neuronal growth in three-dimensional collagen gels as is maintained following plastic compression to form a spinal cord repair conduit. Tissue Eng Part A 16(10):3173–3184
Acknowledgments
The authors thank Kathryn Lee, Kristen Nicholson, and Sonia Kartha for providing panels for the immunohistochemistry images. This work was supported by funding from the National Institutes of Health/National Institute of Arthritis, Musculoskeletal and Skin Diseases (#AR056288 and BIRT Supplement), the Department of Defense (W81XWH-10-1-1002 and W81XWH-10-2-0140), the National Science Foundation (Grant No. 054745), and the Cervical Spine Research Society, as well as the Catherine D. Sharpe and Ashton Foundations.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this chapter
Cite this chapter
Crosby, N.D., Smith, J.R., Winkelstein, B.A. (2015). Pain Biomechanics. In: Yoganandan, N., Nahum, A., Melvin, J. (eds) Accidental Injury. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1732-7_19
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1732-7_19
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-1731-0
Online ISBN: 978-1-4939-1732-7
eBook Packages: MedicineMedicine (R0)