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Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice.
Abstract
Temporomandibular disorder (TMD) pain that involves inflammation and injury in the
temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of
orofacial pain. We recently found that transient receptor potential vanilloid-4 (TRPV4)
in trigeminal ganglion (TG) neurons is upregulated after TMJ inflammation, and TRPV4
co-expresses with calcitonin gene-related peptide (CGRP) in TMJ-innervating TG neurons.
Here, we extended these findings to determine the specific contribution of TRPV4 in
TG neurons to TMD pain, and examine whether sensory neuron-TRPV4 modulates TMD pain
via CGRP. In mouse models of TMJ inflammation or masseter muscle injury, sensory neuron-Trpv4
conditional knockout (cKO) mice displayed reduced pain. Co-expression of TRPV4 and
CGRP in TMJ- or masseter muscle-innervating TG neurons was increased after TMJ inflammation
and masseter muscle injury, respectively. Activation of TRPV4-expressing TG neurons
triggered secretion of CGRP, which was associated with increased levels of CGRP in
peri-TMJ tissues, masseter muscle, spinal trigeminal nucleus, and plasma in both models.
Local injection of CGRP into the TMJ or masseter muscle evoked acute pain in naïve
mice, while blockade of CGRP receptor attenuated pain in mouse models of TMD. These
results suggest that TRPV4 in TG neurons contributes to TMD pain by potentiating CGRP
secretion. Perspective: This study demonstrates that activation of TRPV4 in TG sensory
neurons drives pain by potentiating the release of pain mediator CGRP in mouse models
of TMJ inflammation and masseter muscle injury. Targeting TRPV4 and CGRP may be of
clinical potential in alleviating TMD pain.
Type
Journal articlePermalink
https://hdl.handle.net/10161/26413Published Version (Please cite this version)
10.1016/j.jpain.2022.12.001Publication Info
Suttle, Abbie; Wang, Peng; Dias, Fabiana C; Zhang, Qiaojuan; Luo, Yuhui; Simmons,
Lauren; ... Chen, Yong (2022). Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice. The journal of pain. pp. S1526-5900(22)00462-X. 10.1016/j.jpain.2022.12.001. Retrieved from https://hdl.handle.net/10161/26413.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
Andrey V Bortsov
Assistant Professor in Anesthesiology
Dr. Andrey Bortsov is an Assistant Professor in the Department of Anesthesiology and
holds a faculty position in the Center for Translational Pain Medicine (CTPM). He
earned his Doctor of Medicine degree (1999) from Pavlov State Medical University,
Saint Petersburg, Russia, and his PhD in Epidemiology (2010) from the University of
South Carolina at Columbia.In 2010, he joined the faculty at UNC Department of Anesthesio
Yong Chen
Associate Professor in Neurology
Dr. Yong Chen is an Associate Professor of Neurology at the Duke University School
of Medicine. He is also affiliated with Duke Anesthesiology-Center for Translational
Pain Medicine (CTPM) and Duke-Pathology.
The Chen lab mainly studies sensory neurobiology of pain and itch, with a focus on
TRP ion channels and neural circuits. The main objective of our lab is to identify
molecular and cellular mechanisms underlying chronic pain and chronic-disease associated
itch, using a combi
Andrea Gail Nackley
Associate Professor in Anesthesiology
Pain is a multidimensional sensory and emotional experience that is important for
our survival, but once pain becomes chronic it is no longer beneficial and, instead,
becomes a disorder in and of itself. Chronic pain remains one of our nation’s most
significant healthcare problems due to a limited understanding of the underlying genetic
and environmental factors. There are three main objectives of our lab’s research in
this area:
To determine
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