Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.
Abstract
Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain.
TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness
of its pain, and its largely elusive pathogenesis. Against this background, we sought
to investigate the pathogenetic contributions of the calcium-permeable TRPV4 ion channel,
robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation
and pain behavior. We demonstrate here that TRPV4 is critical for TMJ-inflammation-evoked
pain behavior in mice and that trigeminal ganglion pronociceptive changes are TRPV4-dependent.
As a quantitative metric, bite force was recorded as evidence of masticatory sensitization,
in keeping with human translational studies. In Trpv4(-/-) mice with TMJ inflammation,
attenuation of bite force was significantly less than in wildtype (WT) mice. Similar
effects were seen with systemic application of a specific TRPV4 inhibitor. TMJ inflammation
and mandibular bony changes were apparent after injections of complete Freund adjuvant
but were remarkably independent of the Trpv4 genotype. It was intriguing that, as
a result of TMJ inflammation, WT mice exhibited significant upregulation of TRPV4
and phosphorylated extracellular-signal-regulated kinase (ERK) in TMJ-innervating
trigeminal sensory neurons, which were absent in Trpv4(-/-) mice. Mice with genetically-impaired
MEK/ERK phosphorylation in neurons showed resistance to reduction of bite force similar
to that of Trpv4(-/-) mice. Thus, TRPV4 is necessary for masticatory sensitization
in TMJ inflammation and probably functions upstream of MEK/ERK phosphorylation in
trigeminal ganglion sensory neurons in vivo. TRPV4 therefore represents a novel pronociceptive
target in TMJ inflammation and should be considered a target of interest in human
TMJD.
Type
Journal articleSubject
AnimalsBite Force
Cell Size
Disease Models, Animal
Female
Freund's Adjuvant
Gene Expression Regulation
Glycoproteins
Green Fluorescent Proteins
Inflammation
MAP Kinase Kinase Kinases
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins
Sensory Receptor Cells
Sex Factors
TRPV Cation Channels
Temporomandibular Joint Dysfunction Syndrome
Time Factors
Tomography, X-Ray Computed
Trigeminal Ganglion
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https://hdl.handle.net/10161/12973Published Version (Please cite this version)
10.1016/j.pain.2013.04.004Publication Info
Chen, Yong; Williams, Susan H; McNulty, Amy L; Hong, Ji Hee; Lee, Suk Hee; Rothfusz,
Nicole E; ... Liedtke, Wolfgang (2013). Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.
Pain, 154(8). pp. 1295-1304. 10.1016/j.pain.2013.04.004. Retrieved from https://hdl.handle.net/10161/12973.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yong Chen
Associate Professor of Neurology
Farshid Guilak
Lazlo Ormandy Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Wolfgang Bernhard Liedtke
Adjunct Professor in the Department of Neurology
Research Interests in the Liedtke-Lab:
Pain/ nociception
Sensory transduction and -transmission
TRP ion channels
Water and salt equilibrium regulated by the central nervous system
Visit the lab's website, download papers and read Dr. Liedtke's CV here.
Amy Lynn McNulty
Associate Professor in Orthopaedic Surgery
The McNulty Lab is working to develop strategies to prevent osteoarthritis and to
promote tissue repair and regeneration following joint injury. In order to accomplish
this, we are working in three main areas. 1) We are working to understand the pathways
that are activated by normal and injurious mechanical loading of cartilage and meniscus
and how these mechanotransduction pathways are altered during aging, injury, and tissue
degeneration. A greater understanding of alterations in mech
Carlene D Moore
Assistant Professor in Neurology
Andrea Beth Taylor
Adjunct Professor in the Department of Orthopaedic Surgery
Fan Wang
Morris N. Broad Distinguished Professor
My lab studies neural circuit basis of sensory perception. Specifically we are interested
in determining neural circuits underlying (1) active touch sensation including tactile
processing stream and motor control of touch sensors on the face; (2) pain sensation
including both sensory-discriminative and affective aspects of pain; and (3) general
anesthesia including the active pain-suppression process. We use a combination of
genetic, viral, electrophysiology, and in vivo imaging (in f
Alphabetical list of authors with Scholars@Duke profiles.

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