Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.
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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.
Disease Models, Animal
Gene Expression Regulation
Green Fluorescent Proteins
MAP Kinase Kinase Kinases
Mice, Inbred C57BL
Nerve Tissue Proteins
Sensory Receptor Cells
TRPV Cation Channels
Temporomandibular Joint Dysfunction Syndrome
Tomography, X-Ray Computed
Published Version (Please cite this version)10.1016/j.pain.2013.04.004
Publication InfoChen, Yong; Gereau, RW; Guilak, Farshid; Hong, Ji Hee; Lee, SH; Liedtke, Wolfgang Bernhard; ... Williams, SH (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 http://hdl.handle.net/10161/12973.
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Assistant Professor in Neurology
Lazlo Ormandy Professor of Orthopaedic Surgery
Professor 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.
Assistant Professor in Orthopaedic Surgery
The long term goals of the McNulty lab are to develop strategies to prevent osteoarthritis and to promote tissue repair and regeneration following joint injury. In order to achieve these goals, we need to understand the mechanisms necessary for tissue repair and regeneration and how they are altered with aging and joint injury. Specifically, we are working to enhance the integrative repair of meniscus to restore meniscal function and decrease the risk of osteoarthritis development. &
Assistant Professor of Neurology
Morris N. Broad Distinguished Professor
My lab studies neural circuit basis of sensory perception and motor action.Specifically we are interested in determining functions as well as mapping the meso-scale connectivity of neural circuits involved in (1) voluntary movements; (2) touch and pain sensation; and (3) social interactions. We use a combination of genetic, viral, electrophysiology, and in vivo imaging (in free-moving animals) techniques to study these questions.
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