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Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice.

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Date
2022-12
Authors
Suttle, Abbie
Wang, Peng
Dias, Fabiana C
Zhang, Qiaojuan
Luo, Yuhui
Simmons, Lauren
Bortsov, Andrey
Tchivileva, Inna E
Nackley, Andrea G
Chen, Yong
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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 article
Subject
CGRP
TRPV4
masseter muscle
pain
temporomandibular joint
Permalink
https://hdl.handle.net/10161/26413
Published Version (Please cite this version)
10.1016/j.jpain.2022.12.001
Publication 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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Scholars@Duke

Chen

Yong Chen

Associate Professor in Neurology
Nackley

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
Alphabetical list of authors with Scholars@Duke profiles.
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