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Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.

Publication ,  Journal Article
Suttle, A; Wang, P; Dias, FC; Zhang, Q; Luo, Y; Simmons, L; Bortsov, A; Tchivileva, IE; Nackley, AG; Chen, Y
Published in: J Pain
May 2023

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 coexpresses 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. Coexpression 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.

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Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

May 2023

Volume

24

Issue

5

Start / End Page

782 / 795

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Temporomandibular Joint Disorders
  • TRPV Cation Channels
  • Sensory Receptor Cells
  • Mice
  • Inflammation
  • Facial Pain
  • Calcitonin Gene-Related Peptide
  • Arthritis
  • Animals
 

Citation

APA
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Suttle, A., Wang, P., Dias, F. C., Zhang, Q., Luo, Y., Simmons, L., … Chen, Y. (2023). Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice. J Pain, 24(5), 782–795. https://doi.org/10.1016/j.jpain.2022.12.001
Suttle, Abbie, Peng Wang, Fabiana C. Dias, Qiaojuan Zhang, Yuhui Luo, Lauren Simmons, Andrey Bortsov, Inna E. Tchivileva, Andrea G. Nackley, and Yong Chen. “Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.J Pain 24, no. 5 (May 2023): 782–95. https://doi.org/10.1016/j.jpain.2022.12.001.
Suttle A, Wang P, Dias FC, Zhang Q, Luo Y, Simmons L, et al. Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice. J Pain. 2023 May;24(5):782–95.
Suttle, Abbie, et al. “Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.J Pain, vol. 24, no. 5, May 2023, pp. 782–95. Pubmed, doi:10.1016/j.jpain.2022.12.001.
Suttle A, Wang P, Dias FC, Zhang Q, Luo Y, Simmons L, Bortsov A, Tchivileva IE, Nackley AG, Chen Y. Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice. J Pain. 2023 May;24(5):782–795.
Journal cover image

Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

May 2023

Volume

24

Issue

5

Start / End Page

782 / 795

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Temporomandibular Joint Disorders
  • TRPV Cation Channels
  • Sensory Receptor Cells
  • Mice
  • Inflammation
  • Facial Pain
  • Calcitonin Gene-Related Peptide
  • Arthritis
  • Animals