Research Papers

The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

[+] Author and Article Information
Megan M. Sperry

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: sperrym@seas.upenn.edu

Meagan E. Ita

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: meita@seas.upenn.edu

Sonia Kartha

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: skartha@seas.upenn.edu

Sijia Zhang

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: sijiaz@seas.upenn.edu

Ya-Hsin Yu

Department of Endodontics,
School of Dental Medicine,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: yayu@upenn.edu

Beth Winkelstein

Departments of Bioengineering
and Neurosurgery,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
e-mail: winkelst@seas.upenn.edu

Manuscript received December 10, 2016; final manuscript received December 23, 2016; published online January 19, 2017. Assoc. Editor: Victor H. Barocas.

J Biomech Eng 139(2), 021003 (Jan 19, 2017) (13 pages) Paper No: BIO-16-1509; doi: 10.1115/1.4035647 History: Received December 10, 2016; Revised December 23, 2016

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.

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Fig. 1

Human anatomy and rat computed tomography (CT) three-dimensional reconstructions and Safranin-O staining of tissue sections of the (a) facet joint and (b) TMJ, with important anatomy highlighted: sixth cervical vertebrae (C6), seventh cervical vertebrae (C7), mandibular fossa (MF), articular disk (D), and mandibular condyle (C)

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Fig. 4

Intra-articular NGF injection prior to physiological facet joint loading induces pain, with decreased withdrawal thresholds from baseline (#p < 0.001). The groups receiving only 1 μg of NGF or a nonpainful distraction (vehicle + D2NP) does not develop pain and their withdrawal thresholds are greater than the group receiving NGF prior to physiological loading. (1 μg + D2NP) (*p < 0.05).

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Fig. 3

Collagenase digestion of an in vitro collagen gel system shows that collagenase digestion that is sufficient to (a) reduce collagen fiber content also decreases the failure force (*p = 0.007) and stiffness (*p = 0.024) of the gel when loaded in tension, (b) The microstructural collagen fiber reorganization at failure in the gel under tension is also altered, with the normal reorganization of collagen fibers that is evident at failure being absent and a lower circular variance (CV) (*p = 0.001). A higher CV value indicates fiber realignment toward the loading direction, and (c) The same collagenase treatment also increases the expression of phosphorylated ERK (pERK) after loading in mixed neuronal cultures.

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Fig. 2

Behavioral measurements of pain in the area of the TMJ using techniques to (a) measure mechanical hyperalgesia and (b) quantify the rat grimace scale scoring for spontaneous pain levels. Both behavioral responses are shown relative to sham control responses receiving only exposure to anesthesia. For both assessments, a one-way ANOVA compared groups (n = 4/group), with the chronic exposure being different from the sham response (*p < 0.001; #p = 0.015). Baseline (BL) measurements are taken before any exposures and also serve as a control measurement.

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Fig. 5

In vivo CT imaging of the TMJ showing changes in the overall joint architecture, with (a) more flattening of the TMJ condyle at day 14 with chronic pain than for sham controls and (b) quantification of changes in bone density. Changes in the CT image intensity at day 14 by image subtraction from baseline (BL) show the greatest change from controls in TMJ condyle structure with chronic pain (#p = 0.013).

Grahic Jump Location
Fig. 6

The brain can be represented as a network: a collection of brain regions (nodes; circles) and connections between them (edges; lines). Applying this methodology to TMJ loading-induced pain, modifications in functional modules between baseline and after TMJ loading (day 7) are evident, as highlighted by changes in module-affiliation of brain regions.



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