Yong Chen

Temporomandibular disorders (TMD) include a group of painful conditions that involve the temporomandibular joint (TMJ), the muscles of mastication, and adjacent anatomic structures. In an effort to overcome limitations imposed by shortcomings in pre-clinical pain models of these disorders, we have reverse-translated measurements of bite-force, as a surrogate metric of TMD pain, from human clinical research to the laboratory mouse (Pain. 2013, 154:1295-304). This approach is instrumental in defining the significant role of TRP ion channels in TMD pain.  

Human subjects with craniofacial pain conditions show greater levels of affective distress, environmental stress, somatic symptoms and pain catastrophizing compared with pain-free controls. The emotional toll of craniofacial pain, including TMD, was higher than that of body pain. Using a novel activity-dependent technology “capturing activated neuronal ensembles” (CANE), we, together with a senior PI-Dr. Fan Wang’s group at Duke-Neurobiology, identified a hitherto unknown monosynaptic connection specifically between trigeminal ganglion (TG) sensory neurons and the lateral parabrachial nucleus-nociceptive neurons, which might provide a neural substrate for heightened craniofacial affective pain (Nat Neurosci. 2017, 20:1734-1743). Currently we are investigating how this monosynaptic connection would affect emotional aspects of craniofacial pain.  

Chronic pain caused by arthritis affects millions of people in the US every year. About 25% of adults with arthritis report experiencing severe joint pain related to arthritis. Using behavioral, genetic, and tissue pathological analysis approaches, we have previously delineated an important role of TRPV1 in arthritis pain (Exp Neurol. 2009, 220:383-90; Osteoarthritis Cartilage. 2009, 17:244-51). Collaborating with a variety of groups, we have also identified the mechanosensitive Piezo-1 and -2 ion channels, both expressed in articular cartilage, are critical for the mechanotransduction of chondrocyte in response to injurious mechanical stress (PNAS. 2014, 111:E5114-22; PNAS. 2021,118(13):e2001611118)

Psoriatic arthritis (PsA) is a form of arthritis that affects a significant percentage of people who have psoriasis-a condition that features red patches of skin topped with silvery scales. Most people develop psoriasis first and are later diagnosed with psoriatic arthritis. Joint pain, stiffness and swelling are the main signs and symptoms of psoriatic arthritis. We are interested in developing novel animal models of PsA pain and use the model to determine the underlying mechanisms. 

Treatment for itch (pruritus) associated with systemic disorders represents a severe unmet medical need for patients with cholestatic liver disease, chronic kidney disease, psoriasis, and some forms of lymphoproliferative disorders. Therapeutic recourse is dire because the underlying pathophysiology has remained largely elusive. 

TRP ion channels have been implicated in the molecular mechanisms of peripheral sensory transduction of itch, with experimental studies supporting significant roles for the chemo-irritant receptor TRPA1 and the heat-capsaicin receptor TRPV1 in primary sensory neurons. TRPV4, a widely expressed multimodally-activated channel expressed in both innervated epithelia and sensory neurons, has also been found relevant for experimental itch. Our lab has demonstrated a novel pro-pruritic role of TRPV4 in skin keratinocytes using keratinocyte-specific Trpv4 knockout (KO) animals (J Biol Chem. 2016, 291:10252-62; Gastroenterology. 2021 161(1):301-317) . We are interested in examining whether and how keratinocyte-TRPV4 contributes to chronic disease-associated itch.