Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice.
| dc.contributor.author | Suttle, Abbie | |
| dc.contributor.author | Wang, Peng | |
| dc.contributor.author | Dias, Fabiana C | |
| dc.contributor.author | Zhang, Qiaojuan | |
| dc.contributor.author | Luo, Yuhui | |
| dc.contributor.author | Simmons, Lauren | |
| dc.contributor.author | Bortsov, Andrey | |
| dc.contributor.author | Tchivileva, Inna E | |
| dc.contributor.author | Nackley, Andrea G | |
| dc.contributor.author | Chen, Yong | |
| dc.date.accessioned | 2023-01-02T19:44:02Z | |
| dc.date.available | 2023-01-02T19:44:02Z | |
| dc.date.issued | 2022-12 | |
| dc.date.updated | 2023-01-02T19:44:02Z | |
| dc.description.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. | |
| dc.identifier | S1526-5900(22)00462-X | |
| dc.identifier.issn | 1526-5900 | |
| dc.identifier.issn | 1528-8447 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | The journal of pain | |
| dc.relation.isversionof | 10.1016/j.jpain.2022.12.001 | |
| dc.subject | CGRP | |
| dc.subject | TRPV4 | |
| dc.subject | masseter muscle | |
| dc.subject | pain | |
| dc.subject | temporomandibular joint | |
| dc.title | Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice. | |
| dc.type | Journal article | |
| pubs.begin-page | S1526-5900(22)00462-X | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Pharmacology & Cancer Biology | |
| pubs.organisational-group | Anesthesiology | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Neurology | |
| pubs.organisational-group | Neurology, Headache and Pain | |
| pubs.publication-status | Published |
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