Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain.
Issue Section:
Research Papers
References
1.
NIDCR
, 2014
, “Facial Pain
,” National Institute of Dental and Craniofacial Research, Bethesda, MD, accessed Aug. 3, 2016, http://www.nidcr.nih.gov/datastatistics/finddatabytopic/facialpain/2.
Institute of Medicine of the National Academies
, 2011
, “Relieving Pain in America
,” National Academies Press, Washington DC.3.
Gaskin
, D. J.
, and Richard
, P.
, 2012
, “The Economic Costs of Pain in the United States
,” J. Pain
, 13
(8
), pp. 715
–724
.4.
Turk
, D. C.
, 2002
, “Psychological Factors in Chronic Pain: Evolution and Revolution
,” J. Consult. Clin. Psychol.
, 70
(3
), pp. 678
–690
.5.
Breivik
, H.
, Collett
, B.
, Ventafridda
, V.
, and Cohen
, R.
, 2006
, “Survey of Chronic Pain in Europe: Prevalence, Impact on Daily Life, and Treatment
,” Eur. J. Pain
, 10
(4
), pp. 287
–333
.6.
Hogg-Johnson
, S.
, van der Velde
, G.
, Carroll
, L. J.
, Holm
, L. W.
, Cassidy
, J. D.
, Guzman
, J.
, Frcp
, C.
, Co
, P.
, Haldeman
, S.
, Ammendolia
, C.
, Carragee
, E.
, Hurwitz
, E.
, Nordin
, M.
, Peloso
, P.
, and Frcp
, C.
, 2010
, “The Burden and Determinants of Neck Pain in the General Population Results of the Bone and Joint Decade 2000–2010 Task Force on Neck Pain and Its Associated Disorders
,” Spine
, 33
(4
), pp. 39
–51
.7.
Hussain
, A. M.
, Packota
, G.
, Major
, P. W.
, and Flores-Mir
, C.
, 2008
, “Role of Different Imaging Modalities in Assessment of Temporomandibular Joint Erosions and Osteophytes: A Systematic Review
,” Dentomaxillofacial Radiol.
, 37
(2
), pp. 63
–71
.8.
Scrivani
, S. J.
, Keith
, D. A.
, and Kaban
, L. B.
, 2008
, “Temporomandibular Disorders
,” N. Engl. J. Med.
, 359
(25
), pp. 2693
–2705
.9.
Tanaka
, E.
, Detamore
, M. S.
, and Mercuri
, L. G.
, 2008
, “Degenerative Disorders of the Temporomandibular Joint: Etiology, Diagnosis, and Treatment
,” J. Dent. Res.
, 87
(4
), pp. 296
–307
.10.
Mow
, V. C.
, Ateshian
, G. A.
, and Spilker
, R. L.
, 1993
, “Biomechanics of Diarthrodial Joints: A Review of Twenty Years of Progress
,” ASME J. Biomech. Eng.
, 115
(4B
), pp. 460
–467
.11.
Quinn
, K. P.
, and Winkelstein
, B. A.
, 2007
, “Cervical Facet Capsular Ligament Yield Defines the Threshold for Injury and Persistent Joint-Mediated Neck Pain
,” J. Biomech.
, 40
(10
), pp. 2299
–2306
.12.
Ko
, F. C.
, Dragomir
, C.
, Plumb
, D. A.
, Goldring
, S. R.
, Wright
, T. M.
, Goldring
, M. B.
, and van der Meulen
, M. C. H.
, 2013
, “In Vivo Cyclic Compression Causes Cartilage Degeneration and Subchondral Bone Changes in Mouse Tibiae
,” Arthritis Rheumatol.
, 65
(6
), pp. 1569
–1578
.13.
Kartha
, S.
, Zhou
, T.
, Granquist
, E. J.
, and Winkelstein
, B. A.
, 2016
, “Development of a Rat Model of Mechanically Induced Tunable Pain and Associated Temporomandibular Joint Responses
,” J. Oral Maxillofac. Surg.
, 74
(1
), pp. 54.e1
–54.e10
.14.
Zhang
, S.
, Cao
, X.
, Stablow
, A. M.
, Shenoy
, V. B.
, and Winkelstein
, B. A.
, 2016
, “Tissue Strain Reorganizes Collagen With a Switchlike Response That Regulates Neuronal Extracellular Signal-Regulated Kinase Phosphorylation In Vitro: Implications for Ligamentous Injury and Mechanotransduction
,” ASME J. Biomech. Eng.
, 138
(2
), p. 21013
.15.
Winkelstein
, B.
, 2012
, “How can Animal Models Inform on the Transition to Chronic Symptoms in Whiplash?
” Spine
, 36
(25S
), pp. 1
–16
.16.
Cohen
, S. P.
, Huang
, J. H. Y.
, and Brummett
, C.
, 2013
, “Facet Joint Pain–Advances in Patient Selection and Treatment
,” Nat. Rev. Rheumatol.
, 9
(2
), pp. 101
–116
.17.
Côté
, P.
, van der Velde
, G.
, David Cassidy
, J.
, Carroll
, L. J.
, Hogg-Johnson
, S.
, Holm
, L. W.
, Carragee
, E. J.
, Haldeman
, S.
, Nordin
, M.
, Hurwitz
, E. L.
, Guzman
, J.
, and Peloso
, P. M.
, 2008
, “The Burden and Determinants of Neck Pain in Workers
,” Eur. Spine J.
, 17
(4
), pp. 60
–74
.18.
Lee
, K. E.
, Davis
, M. B.
, Mejilla
, R. M.
, and Winkelstein
, B. A.
, 2004
, “In Vivo Cervical Facet Capsule Distraction: Mechanical Implications for Whiplash & Neck Pain
,” Stapp Car Crash J.
, 48
, pp. 373
–395
.http://spinepain.seas.upenn.edu/Lee2004.pdf19.
Siegmund
, G. P.
, Winkelstein
, B. A.
, Ivancic
, P. C.
, Svensson
, M. Y.
, and Vasavada
, A.
, 2009
, “The Anatomy and Biomechanics of Acute and Chronic Whiplash Injury
,” Traffic Inj. Prev.
, 10
(2
), pp. 101
–112
.20.
Dong
, L.
, Smith
, J. R.
, and Winkelstein
, B. A.
, 2013
, “Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated With Attenuation of Pain After Facet Joint Injury
,” J. Neurotrauma
, 30
(10
), pp. 818
–825
.21.
Cavanaugh
, J. M.
, 2006
, “Pain Generation in Lumbar and Cervical Facet Joints
,” J. Bone Jt. Surg.
, 88
(Suppl 2
), pp. 63
–67
.22.
Jaumard
, N. V.
, Welch
, W. C.
, and Winkelstein
, B. A.
, 2011
, “Spinal Facet Joint Biomechanics and Mechanotransduction in Normal, Injury and Degenerative Conditions
,” ASME J. Biomech. Eng.
, 133
(7
), p. 71010
.23.
Kras
, J. V.
, Kartha
, S.
, and Winkelstein
, B. A.
, 2015
, “Intra-Articular Nerve Growth Factor Regulates Development, But Not Maintenance, of Injury-Induced Facet Joint Pain & Spinal Neuronal Hypersensitivity
,” Osteoarthritis Cartilage
, 23
(11
), pp. 1999
–2008
.24.
Loeser
, J. D.
, and Treede
, R. D.
, 2008
, “The Kyoto Protocol of IASP Basic Pain Terminology
,” Pain
, 137
(3
), pp. 473
–477
.25.
Malfait
, A.-M.
, and Schnitzer
, T. J.
, 2013
, “Towards a Mechanism-Based Approach to Pain Management in Osteoarthritis
,” Nat. Rev. Rheumatol.
, 9
(11
), pp. 654
–664
.26.
Woolf
, C. J.
, 2011
, “Central Sensitization: Implications for the Diagnosis and Treatment of Pain
,” Pain
, 152
(Suppl 3
), pp. S2
–S15
.27.
Bushnell
, M. C.
, Marta
, Č.
, and Low
, L. A.
, 2013
, “Cognitive and Emotional Control of Pain and Its Disruption in Chronic Pain
,” Nat. Rev. Neurosci.
, 14
(7
), pp. 502
–511
.28.
Loeser
, J. D.
, and Melzack
, R.
, 1999
, “Pain: An Overview
,” Lancet
, 353
(9164
), pp. 1607
–1609
.29.
Woolf
, C. J.
, and Salter
, M. W.
, 2000
, “Neuronal Plasticity: Increasing the Gain in Pain
,” Science
, 288
(5472
), pp. 1765
–1769
.30.
Hu
, H.-J.
, and Gereau
, R. W.
, 2003
, “ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons—II: Modulation of Neuronal Excitability
,” J. Neurophysiol.
, 90
(3
), pp. 1680
–1688
.31.
Impey
, S.
, Obrietan
, K.
, and Storm
, D. R.
, 1999
, “Making New Connections: Role of ERK/MAP Kinase Signaling in Neuronal Plasticity
,” Neuron
, 23
(1
), pp. 11
–14
.32.
Schaible
, H. G.
, and Grubb
, B. D.
, 1993
, “Afferent and Spinal Mechanisms of Joint Pain
,” Pain
, 55
(1
), pp. 5
–54
.33.
Syré
, P. P.
, Weisshaar
, C. L.
, and Winkelstein
, B. A.
, 2014
, “Sustained Neuronal Hyperexcitability is Evident in the Thalamus After a Transient Cervical Radicular Injury
,” Spine
, 39
(15
), pp. E870
–E877
.34.
Crosby
, N. D.
, Gilliland
, T. M.
, and Winkelstein
, B. A.
, 2014
, “Early Afferent Activity From the Facet Joint After Painful Trauma to Its Capsule Potentiates Neuronal Excitability and Glutamate Signaling in the Spinal Cord
,” Pain
, 155
(9
), pp. 1878
–1887
.35.
Ita
, M.
, Crosby
, N.
, Bulka
, B.
, and Winkelstein
, B.
, 2016
, “Painful Cervical Facet Joint Injury is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Deferentially Relate to Local Tissue Injury Severity
,” Spine
, 39
(3
), pp. 207
–212
.36.
Winkelstein
, B.
, 2006
, “Pain & Injury: Mechanisms of Central Sensitization, CNS Nociception, Injury Biomechanics, and Implications for Muscuoloskeletal Disorders
,” Occupational Ergonomics Handbook
, CRC Press
, Boca Raton, FL
, pp. 16.1
–16.16
.37.
Yoganandan
, N.
, Knowles
, S. A.
, Maiman
, D. J.
, and Pintar
, F. A.
, 2003
, “Anatomic Study of the Morphology of Human Cervical Facet Joint
,” Spine
, 28
(20
), pp. 2317
–2323
.38.
Louis
, R.
, 1985
, “Spinal Stability as Defined by the Three-Column Spine Concept
,” Anat. Clin.
, 7
(1
), pp. 33
–42
.39.
Pal
, G. P.
, and Sherk
, H. H.
, 1988
, “The Vertical Stability of the Cervical Spine
,” Spine
, 13
(5
), pp. 447
–449
.40.
Mercer
, S.
, and Bogduk
, N.
, 1993
, “Intra-Articular Inclusions of the Cervical Synovial Joints
,” Br. J. Rheumatol.
, 32
(8
), pp. 705
–710
.41.
Yahia
, L.
, and Garzon
, S.
, 1993
, “Structure on the Capsular Ligaments of the Facet Joints
,” Ann. Anat.
, 175
(2
), pp. 185
–188
.42.
Yamashita
, T.
, Minaki
, Y.
, Ozaktay
, A. C.
, Cavanaugh
, J. M.
, and King
, A. I.
, 1996
, “A Morphological Study of the Fibrous Capsule of the Human Lumbar Facet Joint
,” Spine
, 21
(5
), pp. 538
–543
.43.
Sato
, S.
, Oguma
, H.
, Murakami
, G.
, and Noriyasu
, S.
, 2002
, “Morphometrical Study of the Joint Surface and Capsule of the Lumbar Zygapophysial Joint With Special Reference to Their Laterality
,” Okajimas Folia Anat. Jpn.
, 79
(1
), pp. 43
–53
.44.
McLain
, R.
, 1994
, “Mechanoreceptor Endings in Human Cervical Facet Joints
,” Spine
, 19
(5
), pp. 495
–501
.45.
Chen
, C.
, Lu
, Y.
, Kallakuri
, S.
, Patwardhan
, A.
, and Cavanaugh
, J. M.
, 2006
, “Distribution of A-δ and C-Fiber Receptors in the Cervical Facet Joint Capsule
,” J. Bone Jt. Surg.
, 88
(8), pp. 1807
–1816
.46.
Kalichman
, L.
, and Hunter
, D. J.
, 2008
, “The Genetics of Intervertebral Disc Degeneration. Associated Genes
,” Jt., Bone, Spine
, 75
(4
), pp. 388
–396
.47.
Inami
, S.
, Shiga
, T.
, Tsujino
, A.
, Yabuki
, T.
, Okado
, N.
, and Ochiai
, N.
, 2001
, “Immunohistochemical Demonstration of Nerve Fibers in the Synovial Fold of the Human Cervical Facet Joint
,” J. Orthop. Res.
, 19
(4
), pp. 593
–596
.48.
Kallakuri
, S.
, Li
, Y.
, Chen
, C.
, and Cavanaugh
, J. M.
, 2012
, “Innervation of Cervical Ventral Facet Joint Capsule: Histological Evidence
,” World J. Orthop.
, 3
(2
), pp. 10
–14
.49.
Kallakuri
, S.
, Singh
, A.
, Chen
, C.
, and Cavanaugh
, J. M.
, 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
), pp. 1182
–1186
.50.
Kras
, J. V.
, Weisshaar
, C. L.
, Quindlen
, J.
, and Winkelstein
, B. A.
, 2013
, “Brain-Derived Neurotrophic Factor is Upregulated in the Cervical Dorsal Root Ganglia and Spinal Cord and Contributes to the Maintenance of Pain From Facet Joint Injury in the Rat
,” J. Neurosci. Res.
, 91
(10
), pp. 1312
–1321
.51.
Lu
, Y.
, Chen
, C.
, Kallakuri
, S.
, Patwardhan
, A.
, and Cavanaugh
, J. M.
, 2005
, “Neurophysiological and Biomechanical Characterization of Goat Cervical Facet Joint Capsules
,” J. Orthop. Res.
, 23
(4
), pp. 779
–787
.52.
Anderst
, W. J.
, Donaldson
, W. F.
, Lee
, J. Y.
, and Kang
, J. D.
, 2014
, “In Vivo Cervical Facet Joint Capsule Deformation During Flexion-Extension
,” Spine
, 39
(8
), pp. E514
–E520
.53.
Holsgrove
, T. P.
, Jaumard
, N. V.
, Zhu
, N.
, Stiansen
, N. S.
, Welch
, W. C.
, and Winkelstein
, B. A.
, 2016
, “Upper Cervical Spine Loading Simulating a Dynamic Low-Speed Collision Significantly Increases the Risk of Pain Compared to Quasistatic Loading With Equivalent Neck Kinematics
,” ASME J. Biomech. Eng.
, 138
(12
), p. 121006
.54.
Panjabi
, M. M.
, Cholewicki
, J.
, Nibu
, K.
, Grauer
, J.
, and Vahldiek
, M.
, 1998
, “Capsular Ligament Stretches During In Vitro Whiplash Simulations
,” J. Spinal Disord.
, 11
(3
), pp. 227
–232
.http://journals.lww.com/jspinaldisorders/Abstract/1998/06000/Capsular_Ligament_Stretches_During_In_Vitro.9.aspx55.
Pearson
, A. M.
, Ivancic
, P. C.
, Ito
, S.
, and Panjabi
, M. M.
, 2004
, “Facet Joint Kinematics and Injury Mechanisms During Simulated Whiplash
,” Spine
, 29
(4
), pp. 390
–397
.56.
Sundararajan
, S.
, Prasad
, P.
, Demetropoulos
, C. K.
, Tashman
, S.
, Begeman
, P. C.
, Yang
, K. H.
, and King
, A. I.
, 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
, pp. 331
–372
.https://trid.trb.org/view.aspx?id=75531857.
Winkelstein
, B. A.
, Nightingale
, R. W.
, Richardson
, W. J.
, and Myers
, B. S.
, 2000
, “The Cervical Facet Capsule and Its Role in Whiplash Injury: A Biomechanical Investigation
,” Spine
, 25
(10
), pp. 1238
–1246
.58.
Elliott
, J. M.
, Noteboom
, J. T.
, Flynn
, T. W.
, and Sterling
, M.
, 2009
, “Characterization of Acute and Chronic Whiplash-Associated Disorders
,” J. Orthop. Sports Phys. Ther.
, 39
(5
), pp. 312
–323
.59.
Sterling
, M.
, Hodkinson
, E.
, Pettiford
, C.
, Souvlis
, T.
, and Curatolo
, M.
, 2008
, “Psychologic Factors are Related to Some Sensory Pain Thresholds But Not Nociceptive Flexion Reflex Threshold in Chronic Whiplash
,” Clin. J. Pain
, 24
(2
), pp. 124
–130
.60.
Sterling
, M.
, and Kenardy
, J.
, 2008
, “Physical and Psychological Aspects of Whiplash: Important Considerations for Primary Care Assessment
,” Man. Ther.
, 13
(2
), pp. 93
–102
.61.
Lee
, K. E.
, Davis
, M. B.
, and Winkelstein
, B. A.
, 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
), pp. 1383
–1393
.62.
Quinn
, K. P.
, Dong
, L.
, Golder
, F. J.
, and Winkelstein
, B. A.
, 2010
, “Neuronal Hyperexcitability in the Dorsal Horn After Painful Facet Joint Injury
,” Pain
, 151
(2
), pp. 414
–421
.63.
Dong
, L.
, Quindlen
, J. C.
, Lipschutz
, D. E.
, and Winkelstein
, B. A.
, 2012
, “Whiplash-Like Facet Joint Loading Initiates Glutamatergic Responses in the DRG and Spinal Cord Associated With Behavioral Hypersensitivity
,” Brain Res.
, 1461
, pp. 51
–63
.64.
Lee
, K. E.
, Thinnes
, J. H.
, Gokhin
, D. S.
, and Winkelstein
, B. A.
, 2004
, “A Novel Rodent Neck Pain Model of Facet-Mediated Behavioral Hypersensitivity: Implications for Persistent Pain and Whiplash Injury
,” J. Neurosci. Methods
, 137
(2
), pp. 151
–159
.65.
Dong
, L.
, and Winkelstein
, B. A.
, 2010
, “Simulated Whiplash Modulates Expression of the Glutamatergic System in the Spinal Cord Dynamic Cervical Facet Loading
,” J. Neurotrauma
, 27
(1
), pp. 163
–174
.66.
Manchikanti
, L.
, Boswell
, M. V.
, Singh
, V.
, Pampati
, V.
, Damron
, K. S.
, and Beyer
, C. D.
, 2004
, “Prevalence of Facet Joint Pain in Chronic Spinal Pain of Cervical, Thoracic, and Lumbar Regions
,” BMC Musculoskeletal Disord.
, 5
(1
), p. 15
.67.
Norris
, S.
, and Watt
, I.
, 1983
, “The Prognosis of Neck Injuries Resulting From Rear-End Vehicle Collisions
,” J. Bone Jt. Surg.
, 65
(5
), pp. 608
–611
.http://www.bjj.boneandjoint.org.uk/content/65-B/5/608.short68.
Sterling
, M.
, Jull
, G.
, Vicenzino
, B.
, and Kenardy
, J.
, 2003
, “Sensory Hypersensitivity Occurs Soon After Whiplash Injury and is Associated With Poor Recovery
,” Pain
, 104
(3
), pp. 509
–517
.69.
Crosby
, N. D.
, Weisshaar
, C. L.
, and Winkelstein
, B. A.
, 2013
, “Spinal Neuronal Plasticity is Evident Within 1 Day After a Painful Cervical Facet Joint Injury
,” Neurosci. Lett.
, 542
, pp. 102
–106
.70.
Rothman
, S. M.
, Huang
, Z.
, Lee
, K. E.
, Weisshaar
, C. L.
, and Winkelstein
, B. A.
, 2009
, “Cytokine mRNA Expression in Painful Radiculopathy
,” J. Pain
, 10
(1
), pp. 90
–99
.71.
Scott
, D.
, Jull
, G.
, and Sterling
, M.
, 2005
, “Widespread Sensory Hypersensitivity is a Feature of Chronic Whiplash-Associated Disorder But Not Chronic Idiopathic Neck Pain
,” Clin. J. Pain
, 21
(2
), pp. 175
–181
.72.
Takahashi
, Y.
, and Nakajima
, Y.
, 1996
, “Dermatomes in the Rat Limbs as Determined by Antidromic Stimulation of Sensory C-Fibers in Spinal Nerves
,” Pain
, 67
(1
), pp. 197
–202
.73.
Rees
, L. A.
, 1954
, “The Structure and Function of the Mandibular Joint
,” Br. Dent. J.
, 96
(6
), pp. 125
–133
.74.
Bade
, H.
, 1999
, “The Function of the Disco-Muscular Apparatus in the Human Temporomandibular Joint
,” Ann. Anat.
, 181
(1
), pp. 65
–67
.75.
Okeson
, J.
, 2004
, Bell's Orofacial Pains: The Clinical Management of Orofacial Pain
, Quintessence
, Chicago, IL
.76.
Dworkin
, S.
, and Burgess
, J.
, 1987
, “Orofacial Pain of Psychogenic Origin: Current Concepts and Classification
,” J. Am. Dent. Assoc.
, 115
(4
), pp. 565
–571
.77.
Mejersjö
, C.
, and Hollender
, L.
, 1984
, “Radiography of the Temporomandibular Joint in Female Patients With TMJ Pain or Dysfunction. A Seven Year Follow-Up
,” Acta Radiol.: Diagn.
, 25
(3
), pp. 169
–176
.78.
Gallo
, L. M.
, Chiaravalloti
, G.
, Iwasaki
, L. R.
, Nickel
, J. C.
, and Palla
, S.
, 2006
, “Mechanical Work During Stress-Field Translation in the Human TMJ
,” J. Dent. Res.
, 85
(11
), pp. 1006
–1010
.79.
Zarb
, G. A.
, and Carlsson
, G. E.
, 1999
, “Temporomandibular Disorders: Osteoarthritis
,” J. Orofacial Pain
, 13
(4
), pp. 295
–306
.80.
Sessle
, B. J.
, 1999
, “The Neural Basis of Temporomandibular Joint and Masticatory Muscle Pain
,” J. Orofacial Pain
, 13
(4
), pp. 238
–245
.81.
Suzuki
, I.
, Harada
, T.
, Asano
, M.
, Tsuboi
, Y.
, Kondo
, M.
, Gionhaku
, N.
, Kitagawa
, J.
, Kusama
, T.
, and Iwata
, K.
, 2007
, “Phosphorylation of ERK in Trigeminal Spinal Nucleus Neurons Following Passive Jaw Movement in Rats With Chronic Temporomandibular Joint Inflammation
,” J. Orofacial Pain
, 21
(3
), pp. 225
–231
.https://www.ncbi.nlm.nih.gov/pubmed/1771796182.
Younger
, J. W.
, Shen
, Y. F.
, Goddard
, G.
, and Mackey
, S. C.
, 2010
, “Chronic Myofascial Temporomandibular Pain is Associated With Neural Abnormalities in the Trigeminal and Limbic Systems
,” Pain
, 149
(2
), pp. 222
–228
.83.
Wilcox
, S. L.
, Gustin
, S. M.
, Macey
, P. M.
, Peck
, C. C.
, Murray
, G. M.
, and Henderson
, L. A.
, 2015
, “Anatomical Changes Within the Medullary Dorsal Horn in Chronic Temporomandibular Disorder Pain
,” Neuroimage
, 117
, pp. 258
–266
.84.
Harper
, D. E.
, Schrepf
, A.
, and Clauw
, D. J.
, 2016
, “Pain Mechanisms and Centralized Pain in Temporomandibular Disorders
,” J. Dent. Res.
, 95
(10
), pp. 1102
–1108
.85.
Hawkins
, J. L.
, and Durham
, P. L.
, 2016
, “Prolonged Jaw Opening Promotes Nociception and Enhanced Cytokine Expression
,” J. Oral Facial Pain Headache
, 30
(1
), pp. 34
–41
.86.
Nicoll
, S. B.
, Hee
, C. K.
, Davis
, M. B.
, and Winkelstein
, B. A.
, 2010
, “A Rat Model of Temporomandibular Joint Pain With Histopathologic Modifications
,” J. Orofacial Pain
, 24
(3
), pp. 298
–304
.http://spinepain.seas.upenn.edu/Nicoll_2010.pdf87.
Tanaka
, E.
, Aoyama
, J.
, Miyauchi
, M.
, Takata
, T.
, Hanaoka
, K.
, Iwabe
, T.
, and Tanne
, K.
, 2005
, “Vascular Endothelial Growth Factor Plays an Important Autocrine/Paracrine Role in the Progression of Osteoarthritis
,” Histochem. Cell Biol.
, 123
(3
), pp. 275
–281
.88.
De Rantere
, D.
, Schuster
, C. J.
, Reimer
, J. N.
, and Pang
, D. S. J.
, 2016
, “The Relationship Between the Rat Grimace Scale and Mechanical Hypersensitivity Testing in Three Experimental Pain Models
,” Eur. J. Pain
, 20
(3
), pp. 417
–426
.89.
Sotocinal
, S. G.
, Sorge
, R. E.
, Zaloum
, A.
, Tuttle
, A. H.
, Martin
, L. J.
, Wieskopf
, J. S.
, Mapplebeck
, J. C.
, Wei
, P.
, Zhan
, S.
, Zhang
, S.
, McDougall
, J. J.
, King
, O. D.
, and Mogil
, J. S.
, 2011
, “The Rat Grimace Scale: A Partially Automated Method for Quantifying Pain in the Laboratory Rat Via Facial Expressions
,” Mol. Pain
, 7
(1
), p. 55
.90.
Benito
, M.
, Veale
, D.
, FitzGerald
, O.
, van den Berg
, W. B.
, and Bresnihan
, B.
, 2005
, “Synovial Tissue Inflammation in Early and Late Osteoarthritis
,” Ann. Rheum. Dis.
, 64
(9
), pp. 1263
–1267
.91.
Bechtold
, T. E.
, Saunders
, C.
, Decker
, R. S.
, Um
, H.
, Bin
, Cottingham
, N.
, Salhab
, I.
, Kurio
, N.
, Billings
, P. C.
, Pacifici
, M.
, Nah
, H. D.
, and Koyama
, E.
, 2016
, “Osteophyte Formation and Matrix Mineralization in a TMJ Osteoarthritis Mouse Model are Associated With Ectopic Hedgehog Signaling
,” Matrix Biol.
, 52–54
, pp. 339
–354
.92.
Wang
, X. D.
, Kou
, X. X.
, Mao
, J. J.
, Gan
, Y. H.
, and Zhou
, Y. H.
, 2012
, “Sustained Inflammation Induces Degeneration of the Temporomandibular Joint
,” J. Dent. Res.
, 91
(5
), pp. 499
–505
.93.
Shen
, P.
, Jiao
, Z.
, Zheng
, J. S.
, Xu
, W. F.
, Zhang
, S. Y.
, Qin
, A.
, and Yang
, C.
, 2015
, “Injecting Vascular Endothelial Growth Factor Into the Temporomandibular Joint Induces Osteoarthritis in Mice
,” Sci. Rep.
, 5
, p. 16244
.94.
Yeh
, T.-T.
, Wen
, Z.-H.
, Lee
, H.-S.
, Lee
, C.-H.
, Yang
, Z.
, Jean
, Y.-H.
, Wu
, S.-S.
, Nimni
, M. E.
, and Han
, B.
, 2008
, “Intra-Articular Injection of Collagenase Induced Experimental Osteoarthritis of the Lumbar Facet Joint in Rats
,” Eur. Spine J.
, 17
(5
), pp. 734
–742
.95.
Gong
, K.
, Shao
, W.
, Chen
, H.
, Wang
, Z.
, and Luo
, Z. J.
, 2011
, “Rat Model of Lumbar Facet Joint Osteoarthritis Associated With Facet-Mediated Mechanical Hyperalgesia Induced by Intra-Articular Injection of Monosodium Iodoacetate
,” J. Formosan Med. Assoc.
, 110
(3
), pp. 145
–152
.96.
Loeser
, R. F.
, Goldring
, S. R.
, Scanzello
, C. R.
, and Goldring
, M. B.
, 2012
, “Osteoarthritis: A Disease of the Joint as an Organ
,” Arthritis Rheumatol.
, 64
(6
), pp. 1697
–1707
.97.
Gellhorn
, A. C.
, Katz
, J. N.
, and Suri
, P.
, 2012
, “Osteoarthritis of the Spine: The Facet Joints
,” Nat. Rev. Rheumatol.
, 9
(4
), pp. 216
–224
.98.
Neogi
, T.
, 2014
, “The Epidemiology and Impact of Pain in Osteoarthritis
,” Osteoarthritis Cartilage
, 21
(9
), pp. 1145
–1153
.99.
Perrot
, S.
, 2015
, “Best Practice & Research Clinical Rheumatology Osteoarthritis Pain
,” Best Pract. Res., Clin. Rheumatol.
, 29
(1
), pp. 90
–97
.100.
Malfait
, A. M.
, Little
, C. B.
, and McDougall
, J. J.
, 2013
, “A Commentary on Modelling Osteoarthritis Pain in Small Animals
,” Osteoarthritis Cartilage
, 21
(9
), pp. 1316
–1326
.101.
Boszczyk
, B.
, Boszczyk
, A.
, Korge
, A.
, Grillhost
, A.
, Boos
, W.
, Putz
, R.
, Milz
, S.
, and Benjamin
, M.
, 2003
, “Immunohistochemical Analysis of the Extracellular Matrix in the Posterior Capsule of the Zygapophysial Joints in Patients With Degenerative L4–5 Motion Segment Instability
,” J. Neurosurg.
, 99
(1
), pp. 27
–33
.http://thejns.org/doi/abs/10.3171/spi.2003.99.1.0027102.
Kim
, J.
, Ahmadinia
, K.
, Li
, X.
, Hamilton
, J. L.
, Andrews
, S.
, Haralampus
, A.
, Xiao
, G.
, Sohn
, H.
, You
, J.
, Seo
, Y.
, and Gary
, S.
, 2015
, “Development of an Experimental Animal Model For Lower Back Pain By Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis
,” J. Cell. Physiol.
, 230
(11
), pp. 2837
–2847
.103.
Shuang
, F.
, Zhu
, J.
, Song
, K.
, Hou
, S.
, Liu
, Y.
, Zhang
, C.
, and Tang
, J.
, 2014
, “Establishment of a Rat Model of Adjuvant-Induced Osteoarthritis of the Lumbar Facet Joint
,” Cell Biochem. Biophys.
, 70
(3
), pp. 1545
–1551
.104.
Kuroki
, Y.
, Honda
, K.
, Kijima
, N.
, Wada
, T.
, Arai
, Y.
, Matsumoto
, N.
, Iwata
, K.
, and Shirakawa
, T.
, 2011
, “In Vivo Morphometric Analysis of Inflammatory Condylar Changes in Rat Temporomandibular Joint
,” Oral Dis.
, 17
(5
), pp. 499
–507
.105.
Ikeda
, Y.
, Yonemitsu
, I.
, Takei
, M.
, Shibata
, S.
, and Ono
, T.
, 2014
, “Mechanical Loading Leads to Osteoarthritis-Like Changes in the Hypofunctional Temporomandibular Joint in Rats
,” Arch. Oral Biol.
, 59
(12
), pp. 1368
–1376
.106.
Loeser
, R. F.
, 2009
, “Aging and Osteoarthritis: the Role of Chondrocyte Senescence and Aging Changes in the Cartilage Matrix
,” Osteoarthritis Cartilage
, 17
(8
), pp. 971
–979
.107.
Iatridis
, J. C.
, Setton
, L. A.
, Foster
, R. J.
, Rawlins
, B. A.
, Weidenbaum
, M.
, and Mow
, V. C.
, 1998
, “Degeneration Affects the Anisotropic and Nonlinear Behaviors of Human Anulus Fibrosus in Compression
,” J. Biomech.
, 31
(6
), pp. 535
–544
.108.
Mort
, J. S.
, and Billington
, C. J.
, 2001
, “Articular Cartilage and Changes in Arthritis: Matrix Degradation
,” Arthritis Res. & Therapy
, 3
(6
), pp. 337
–341
.109.
Song
, R. H.
, Tortorella
, M. D.
, Malfait
, A. M.
, Alston
, J. T.
, Yang
, Z.
, Arner
, E. C.
, and Griggs
, D. W.
, 2007
, “Aggrecan Degradation in Human Articular Cartilage Explants is Mediated by Both ADAMTS-4 and ADAMTS-5
,” Arthritis Rheumatol.
, 56
(2
), pp. 575
–585
.110.
Pearle
, A. D.
, Warren
, R. F.
, and Rodeo
, S. A.
, 2005
, “Basic Science of Articular Cartilage and Osteoarthritis
,” Clin. Sports Med.
, 24
(1
), pp. 1
–12
.111.
Grant
, T.
, Chen
, C.
, Czernuszka
, J.
, and Thompson
, M.
, 2015
, “The Mechanical, Structural, and Compositional Changes of Tendon Exposed to Elastase
,” Ann. Biomed. Eng.
, 43
(10
), pp. 2477
–2486
.112.
Barbir
, A.
, Michalek
, A. J.
, Abbott
, R. D.
, and Iatridis
, J. C.
, 2010
, “Effects of Enzymatic Digestion on Compressive Properties of Rat Intervertebral Discs
,” J. Biomech.
, 43
(6
), pp. 1067
–1073
.113.
Grenier
, S.
, Bhargava
, M. M.
, and Torzilli
, P. A.
, 2014
, “An In Vitro Model for the Pathological Degradation of Articular Cartilage in Osteoarthritis
,” J. Biomech.
, 47
(3
), pp. 645
–652
.114.
Adaes
, S.
, Ferreira-Gomes
, J.
, Mendonca
, M.
, Almeida
, L.
, Castro-Lopes
, J.
, and Neto
, F.
, 2015
, “Injury of Primary Afferent Neurons May Contribute to Osteoarthritis Induced Pain: An Experimental Study Using the Collagenase Model in Rats
,” Osteoarthritis Cartilage
, 23
(6
), pp. 914
–924
.115.
Hill
, C. L.
, Seo
, G. S.
, Gale
, D.
, Totterman
, S.
, Gale
, M. E.
, and Felson
, D. T.
, 2005
, “Cruciate Ligament Integrity in Osteoarthritis of the Knee
,” Arthritis Rheumatol.
, 52
(3
), pp. 794
–799
.116.
Usoskin
, D.
, Zilberter
, M.
, Linnarsson
, S.
, Hjerling-Leffler
, J.
, Uhlén
, P.
, Harkany
, T.
, and Ernfors
, P.
, 2010
, “En Masse in vitro Functional Profiling of the Axonal Mechanosensitivity of Sensory Neurons
,” Proc. Natl. Acad. Sci. U. S. A.
, 107
(37
), pp. 16336
–16341
.117.
Hao
, J.
, and Delmas
, P.
, 2010
, “Multiple Desensitization Mechanisms of Mechanotransducer Channels Shape Firing of Mechanosensory Neurons
,” J. Neurosci.
, 30
(40
), pp. 13384
–13395
.118.
Dong
, L.
, Odeleye
, A. O.
, Jordan-Sciutto
, K. L.
, and Winkelstein
, B. A.
, 2008
, “Painful Facet Joint Injury Induces Neuronal Stress Activation in the DRG: Implications for Cellular Mechanisms of Pain
,” Neurosci. Lett.
, 443
(2
), pp. 90
–94
.119.
Torres
, L.
, Dunlop
, D. D.
, Peterfy
, C.
, Guermazi
, A.
, Prasad
, P.
, Hayes
, K. W.
, Song
, J.
, Cahue
, S.
, Chang
, A.
, Marshall
, M.
, and Sharma
, L.
, 2006
, “The Relationship Between Specific Tissue Lesions and Pain Severity in Persons With Knee Osteoarthritis
,” Osteoarthritis Cartilage
, 14
(10
), pp. 1033
–1040
.120.
Miller
, R. E.
, Miller
, R. J.
, and Malfait
, A. M.
, 2014
, “Osteoarthritis Joint Pain: The Cytokine Connection
,” Cytokine
, 70
(2
), pp. 185
–193
.121.
van der Kraan
, P. M.
, Vitters
, E. L.
, van de Putte
, L. B.
, and van den Berg
, W. B.
, 1989
, “Development of Osteoarthritic Lesions in Mice by ‘Metabolic’ and ‘Mechanical’ Alterations in the Knee Joints
,” Am. J. Pathol.
, 135
(6
), pp. 1001
–1014
.http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1880494&blobtype=pdf122.
Cheng
, J.-K.
, and Ji
, R.-R.
, 2008
, “Intracellular Signaling in Primary Sensory Neurons and Persistent Pain
,” Neurochem. Res.
, 33
(10
), pp. 1970
–1978
.123.
Joseph
, E. K.
, and Levine
, J. D.
, 2010
, “Hyperalgesic Priming is Restricted to Isolectin B4-Positive Nociceptors
,” Neuroscience
, 169
(1
), pp. 431
–435
.124.
Sheon
, R. P.
, 1997
, “Repetitive Strain Injury. 2. Diagnostic and Treatment Tips on Six Common Problems. The Goff Group
,” Postgrad. Med.
, 102
(4
), pp. 72
–78, 81, 85
.125.
Reichling
, D. B.
, and Levine
, J. D.
, 2009
, “Critical Role of Nociceptor Plasticity in Chronic Pain
,” Trends Neurosci.
, 32
(12
), pp. 611
–618
.126.
Aley
, K. O.
, Messing
, R. O.
, Mochly-Rosen
, D.
, and Levine
, J. D.
, 2000
, “Chronic Hypersensitivity for Inflammatory Nociceptor Sensitization Mediated by the Epsilon Isozyme of Protein Kinase C
,” J. Neurosci.
, 20
(12
), pp. 4680
–4685
.http://www.jneurosci.org/content/20/12/4680.long127.
Parada
, C. A.
, Yeh
, J. J.
, Joseph
, E. K.
, and Levine
, J. D.
, 2003
, “Tumor Necrosis Factor Receptor Type-1 in Sensory Neurons Contributes to Induction of Chronic Enhancement of Inflammatory Hyperalgesia in Rat
,” Eur. J. Neurosci.
, 17
(9
), pp. 1847
–1852
.128.
Kras
, J. V.
, Weisshaar
, C. L.
, Pall
, P. S.
, and Winkelstein
, B. A.
, 2015
, “Pain From Intra-Articular NGF or Joint Injury in the Rat Requires Contributions From Peptidergic Joint Afferents
,” Neurosci. Lett.
, 604
, pp. 193
–198
.129.
Hoheisel
, U.
, Unger
, T.
, and Mense
, S.
, 2007
, “Sensitization of Rat Dorsal Horn Neurons by NGF-Induced Subthreshold Potentials and Low-Frequency Activation. A Study Employing Intracellular Recordings in vivo
,” Brain Res.
, 1169
, pp. 34
–43
.130.
Barthel
, C.
, Yeremenko
, N.
, Jacobs
, R.
, Schmidt
, R. E.
, Bernateck
, M.
, Zeidler
, H.
, Tak
, P.
, Baeten
, D.
, and Rihl
, M.
, 2009
, “Nerve Growth Factor and Receptor Expression in Rheumatoid Arthritis and Spondyloarthritis
,” Arthritis Res. Ther.
, 11
(3
), pp. 1
–9
.131.
Orita
, S.
, Ishikawa
, T.
, Miyagi
, M.
, Ochiai
, N.
, Inoue
, G.
, and Eguchi
, Y.
, 2011
, “Pain-Related Sensory Innervation in Monoiodoacetate-Induced Osteoarthritis in Rat Knees That Gradually Develops Neuronal Injury in Addition to Inflammatory Pain
,” BMC Musculoskeletal Disord.
, 12
(134
), pp. 1
–12
.132.
Kras
, J. V.
, Tanaka
, K.
, Gilliland
, T. M.
, and Winkelstein
, B. A.
, 2013
, “An Anatomical and Immunohistochemical Characterization of Afferents Innervating the C6-C7 Facet Joint After Painful Joint Loading in the Rat
,” Spine
, 38
(6
), pp. E325
–E331
.133.
Merighi
, A.
, Carmignoto
, G.
, Gobbo
, S.
, Lossi
, L.
, Salio
, C.
, Vergnano
, A. M.
, and Zonta
, M.
, 2004
, “Neurotrophins in Spinal Cord Nociceptive Pathways
,” Prog. Brain Res.
, 146
, pp. 291
–321
.134.
Mcmahon
, S. B.
, 2016
, “NGF as a Mediator of Inflammatory Pain
,” R. Soc. Philos. Trans. Biol. Sci.
, 351
(1338
), pp. 431
–440
.135.
Mcnamee
, K. E.
, Burleigh
, A.
, Gompels
, L. L.
, Feldmann
, M.
, Allen
, S. J.
, Williams
, R. O.
, Dawbarn
, D.
, Vincent
, T. L.
, and Inglis
, J. J.
, 2010
, “Treatment of Murine Osteoarthritis With TrkAd5 Reveals a Pivotal Role for Nerve Growth Factor in Non-Inflammatory Joint Pain
,” Pain
, 149
(2
), pp. 386
–392
.136.
Crosby
, N. D.
, Zaucke
, F.
, Kras
, J. V.
, Dong
, L.
, Luo
, Z. D.
, and Winkelstein
, B. A.
, 2015
, “Thrombospondin-4 and Excitatory Synaptogenesis Promote Spinal Sensitization After Painful Mechanical Joint Injury
,” Exp. Neurol.
, 264
, pp. 111
–120
.137.
Lee
, K. E.
, and Winkelstein
, B. A.
, 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
), pp. 436
–445
.138.
Vincent
, K. R.
, Conrad
, B. P.
, Fregly
, B. J.
, and Vincent
, H. K.
, 2012
, “The Pathophysiology of Osteoarthritis: A Mechanical Perspective on the Knee Joint
,” PM&R
, 4
(5 Suppl.
), pp. S3
–S9
.139.
Bogduk
, N.
, 2011
, “On Cervical Zygapophysial Joint Pain After Whiplash
,” Spine
, 36
(25S
), pp. 194
–199
.140.
Siegmund
, G. P.
, Myers
, B. S.
, Davis
, M. B.
, Bohnet
, H. F.
, and Winkelstein
, B. A.
, 2001
, “Mechanical Evidence of Cervical Facet Capsule Injury During Whiplash
,” Spine
, 26
(19
), pp. 2095
–2101
.141.
Quinn
, K. P.
, Lee
, K. E.
, Ahaghotu
, C. C.
, and Winkelstein
, B. A.
, 2007
, “Structural Changes in the Cervical Facet Capsular Ligament: Potential Contributions to Pain Following Subfailure Loading
,” Stapp Car Crash J.
, 51
, pp. 169
–187
.http://www.seas.upenn.edu/~winkelst/Quinn_2007.pdf142.
Quinn
, K. P.
, and Winkelstein
, B. A.
, 2008
, “Altered Collagen Fiber Kinematics Define the Onset of Localized Ligament Damage During Loading
,” J. Appl. Physiol.
, 105
(6
), pp. 1881
–1888
.143.
Quinn
, K. P.
, and Winkelstein
, B. A.
, 2009
, “Vector Correlation Technique for Pixel-Wise Detection of Collagen Fiber Realignment During Injurious Tensile Loading
,” J. Biomed. Opt.
, 14
(5
), pp. 54010-1
–54010-10
.144.
Khalsa
, P.
, Hoffman
, A.
, and Grigg
, P.
, 1996
, “Mechanical States Encoded by Stretch-Sensitive Neurons in Feline Joint Capsule
,” J. Neurophysiol.
, 76
(1
), pp. 175
–187
.http://jn.physiology.org/content/76/1/175145.
Kallakuri
, S.
, Singh
, A.
, Lu
, Y.
, Chen
, C.
, Patwardhan
, A.
, and Cavanaugh
, J. M.
, 2008
, “Tensile Stretching of Cervical Facet Joint Capsule and Related Axonal Changes
,” Eur. Spine J.
, 17
(4
), pp. 556
–563
.146.
Weishaupt
, D.
, Zanetti
, M.
, Boos
, N.
, and Hodler
, J.
, 1999
, “MR Imaging and CT in Osteoarthritis of the Lumbar Facet Joints
,” Skeletal Radiol.
, 28
(4
), pp. 215
–219
.147.
Tsiklakis
, K.
, Syriopoulos
, K.
, and Stamatakis
, H. C.
, 2004
, “Radiographic Examination of the Temporomandibular Joint Using Cone Beam Computed Tomography
,” Dentomaxillofacial Radiol.
, 33
(3
), pp. 196
–201
.148.
Pathria
, M.
, Sartoris
, D. J.
, and Resnick
, D.
, 1987
, “Osteoarthritis of the Facet Joints: Accuracy of Oblique Radiographic Assessment
,” Radiology
, 164
(1
), pp. 227
–230
.149.
Duan
, C. Y.
, Espinoza Orías
, A. A.
, Shott
, S.
, An
, H. S.
, Andersson
, G. B. J.
, Hu
, J. Z.
, Lu
, H. B.
, and Inoue
, N.
, 2011
, “In Vivo Measurement of the Subchondral Bone Thickness of Lumbar Facet Joint Using Magnetic Resonance Imaging
,” Osteoarthritis Cartilage
, 19
(1
), pp. 96
–102
.150.
Jaumard
, N. V.
, Udupa
, J. K.
, Welch
, W. C.
, and Winkelstein
, B. A.
, 2014
, “Kinematic Magnetic Resonance Imaging to Define the Cervical Facet Joint Space for the Spine in Neutral and Torsion
,” Spine
, 39
(8
), pp. 664
–672
.151.
Brooks
, S. L.
, Wesresson
, P.-L.
, Eriksson
, L.
, Hansson
, L. G.
, and Barsotti
, J. B.
, 1992
, “Prevalence of Osseous Changes in the Temporomandibular Joint of Asymptomatic Persons Without Internal Derangement
,” Oral Surg., Oral Med., Oral Pathol.
, 73
(1
), pp. 118
–122
.152.
Rohlin
, M.
, Westesson
, P. L.
, and Eriksson
, L.
, 1985
, “The Correlation of Temporomandibular Joint Sounds With Joint Morphology in Fifty-Five Autopsy Specimens
,” J. Oral Maxillofac. Surg.
, 43
(3
), pp. 194
–200
.153.
Kircos
, L. T.
, Ortendahl
, D. A.
, Mark
, A. S.
, and Arakawa
, M.
, 1987
, “Magnetic Resonance Imaging of the TMJ Disc in Asymptomatic Volunteers
,” J. Oral Maxillofac. Surg.
, 45
(10
), pp. 852
–854
.154.
Katzberg
, R. W.
, Tallents
, R. H.
, and Drake
, M.
, 1996
, “Anatomic Disorders of the Temporomandibular Joint Disc in Asymptomatic Subjects
,” J. Oral Maxillofac. Surg.
, 54
(2
), pp. 147
–153
.155.
Lee
, J. W.
, Lee
, S. M.
, Kim
, S. J.
, Choi
, J. W.
, and Baek
, K. W.
, 2013
, “Clinical Utility of Fluoride-18 Positron Emission Tomography/CT in Temporomandibular Disorder With Osteoarthritis: Comparisons With 99mTc-MDP Bone Scan
,” Dentomaxillofacial Radiol.
, 42
(2
), pp. 1
–8
.156.
Nakamura
, H.
, Masuko
, K.
, Yudoh
, K.
, Kato
, T.
, Nishioka
, K.
, Sugihara
, T.
, and Beppu
, M.
, 2007
, “Positron Emission Tomography With 18F-FDG in Osteoarthritic Knee
,” Osteoarthritis Cartilage
, 15
(6
), pp. 673
–681
.157.
Paquet
, J.
, Maskali
, F.
, Poussier
, S.
, Scala
, J.
, and Pinzano
, A.
, 2010
, “Evaluation of a Rat Knee Mono-Arthritis Using MicroPET
,” Biomed. Mater. Eng.
, 20
(3–4
), pp. 195
–202
.158.
Kim
, J. H.
, Kim
, Y. K.
, Kim
, S. G.
, Yun
, P. Y.
, Kim
, J. D.
, and Min
, J. H.
, 2012
, “Effectiveness of Bone Scans in the Diagnosis of Osteoarthritis of the Temporomandibular Joint
,” Dentomaxillofacial Radiol.
, 41
(3
), pp. 224
–229
.159.
Guermazi
, A.
, Roemer
, F. W.
, Haugen
, I. K.
, Crema
, M. D.
, and Hayashi
, D.
, 2013
, “MRI-Based Semiquantitative Scoring of Joint Pathology in Osteoarthritis
,” Nat. Rev. Rheumatol.
, 9
(4
), pp. 236
–251
.160.
Czervionke
, L. F.
, and Fenton
, D. S.
, 2008
, “Fat-Saturated MR Imaging in the Detection of Inflammatory Facet Arthropathy (Facet Synovitis) in the Lumbar Spine
,” Pain Med.
, 9
(4
), pp. 400
–406
.161.
Lakadamyali
, H.
, Tarhan
, N.
, Ergun
, T.
, Cakir
, B.
, and Agildere
, A.
, 2008
, “STIR Sequence for Depiction of Degenerative Changes in Posterior Stabilizing Elements in Patients With Lower Back Pain
,” Musculoskeletal Imaging
, 191
(4
), pp. 973
–979
.http://www.ajronline.org/doi/abs/10.2214/AJR.07.2829162.
Suenaga
, S.
, Hamamoto
, S.
, Kawano
, K.
, Higashida
, Y.
, and Noikura
, T.
, 1996
, “Dynamic MR Imaging of the Temporomandibular Joint in Patients With Arthrosis
,” Am. J. Roentgenol.
, 166
(6
), pp. 1475
–1481
.163.
Kortekaas
, M. C.
, Kwok
, W.
, Reijnierse
, M.
, and Kloppenburg
, M.
, 2015
, “Inflammatory Ultrasound Features Show Independent Associations With Progression of Structural Damage After Over 2 Years of Follow-Up in Patients With Hand Osteoarthritis
,” Ann. Rheum. Dis.
, 74
(9
), pp. 1720
–1724
.164.
Mathiessen
, A.
, Slatkowsky-Christensen
, B.
, Kvien
, T. K.
, Hammer
, H. B.
, and Haugen
, I. K.
, 2016
, “Ultrasound-Detected Inflammation Predicts Radiographic Progression in Hand Osteoarthritis After 5 Years
,” Ann. Rheum. Dis.
, 75
(5
), pp. 825
–830
.165.
Baliki
, M. N.
, Mansour
, A. R.
, Baria
, A. T.
, and Apkarian
, A. V.
, 2014
, “Functional Reorganization of the Default Mode Network Across Chronic Pain Conditions
,” Plos One
, 9
(9
), p. 106133
.166.
Baliki
, M. N.
, Chang
, P. C.
, Baria
, A. T.
, Centeno
, M. V.
, and Apkarian
, A. V.
, 2014
, “Resting-Sate Functional Reorganization of the Rat Limbic System Following Neuropathic Injury
,” Sci. Rep.
, 4
, p. 6186
.167.
Kim
, C.-E.
, Kim
, Y. K.
, Chung
, G.
, Jeong
, J. M.
, Lee
, D. S.
, Kim
, J.
, and Kim
, S. J.
, 2014
, “Large-Scale Plastic Changes of the Brain Network in an Animal Model of Neuropathic Pain
,” Neuroimage
, 98
, pp. 203
–215
.168.
Parks
, E. L.
, Geha
, P. Y.
, Baliki
, M. N.
, Katz
, J.
, Schnitzer
, T. J.
, and Apkarian
, A. V.
, 2011
, “Brain Activity for Chronic Knee Osteoarthritis: Dissociating Evoked Pain From Spontaneous Pain
,” Eur. J. Pain
, 15
(8
), pp. 843.e1
–14
.169.
Youssef
, A. M.
, Gustin
, S. M.
, Nash
, P. G.
, Reeves
, J. M.
, Petersen
, E. T.
, Peck
, C. C.
, Murray
, G. M.
, and Henderson
, L. A.
, 2014
, “Differential Brain Activity in Subjects With Painful Trigeminal Neuropathy and Painful Temporomandibular Disorder
,” Pain
, 155
(3
), pp. 467
–475
.170.
Sperry
, M. M.
, Kartha
, S.
, Granquist
, E. J.
, and Winkelstein
, B. A.
, 2016
, “Meso-Scale Reorganization of Metabolic Brain Networks is Associated With Persistent TMJ Pain
,” SB3C Conference
, Paper No. 59.171.
Reichardt
, J.
, and Bornholdt
, S.
, 2006
, “Statistical Mechanics of Community Detection
,” Phys. Rev. E
, 74
(1
), pp. 1
–16
.172.
Blondel
, V. D.
, Guillaume
, J.-L.
, Lambiotte
, R.
, and Lefebvre
, E.
, 2008
, “Fast Unfolding of Communities in Large Networks
,” J. of Statistical Mechanics: Theory & Experiment
, 2008
(10
), p. P10008
.173.
Rubinov
, M.
, and Sporns
, O.
, 2010
, “Complex Network Measures of Brain Connectivity: Uses and Interpretations
,” Neuroimage
, 52
(3
), pp. 1059
–1069
.174.
Churchill
, J. D.
, Arnold
, L. L.
, and Garraghty
, P. E.
, 2001
, “Somatotopic Reorganization in the Brainstem and Thalamus Following Peripheral Nerve Injury in Adult Primates
,” Brain Res.
, 910
(1
), pp. 142
–152
.Copyright © 2017 by ASME
You do not currently have access to this content.
