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bioRxiv · 10.1101/2025.06.11.659119

Innervation of Retrodiscal Tissues in Patients with Temporomandibular Joint Disorder

Alfaro, J. J.·Hovhannisyan, A. H.·Locke, E. E.·Amarista, F. J.·Perez, D. E.·Akopian, A. N.
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Abstract

Temporomandibular joint (TMJ) disorders (TMJDs) are a group of musculoskeletal conditions affecting the orofacial region and often associated with facial pain. Understanding the sensory innervation of TMJ structures, particularly the retrodiscal tissue, is essential for identifying pain mechanisms in TMJD because to study these mechanisms, we must first determine the sensory neuronal makeup of the TMJ. However, data on nerve types within TMJ tissues remain limited. This study examined the sensory and sympathetic nerve profiles in retrodiscal tissues from TMJD patients with osteoarthritis (OA), rheumatoid arthritis (RA), or condylar hyperplasia (CH) who underwent bilateral TMJ replacement (TMJR). Immunohistochemistry with specific nerve markers was used to visualize and quantify nerve subtypes. CH tissues had significantly lower densities of pgp9.5+ sensory fibers compared to RA and OA, which showed similar levels. Across all subtypes, the ratio of unmyelinated (pgp9.5+/NFH-) to myelinated (pgp9.5+/NFH+) fibers was approximately 70:30. Most sensory nerves were CGRP+ (peptidergic), while a smaller portion were CGRP- (non-peptidergic), some of which were parvalbumin-positive (PV+). Both myelinated and non-myelinated peptidergic as well as non-peptidergic fibers were present in the retrodiscal tissues. In addition to sensory innervation, all retrodiscal tissues contained tyrosine hydroxylase-positive (TH+) sympathetic fibers, primarily innervating blood vessels (alpha-smooth muscle actin (-SMA+)). These vessels were also predominantly innervated by unmyelinated sensory fibers, with limited input from myelinated sensory nerves. In summary, all TMJD subtypes shared similar nerve compositions, but CH tissues exhibited reduced sensory nerve density, a potential explanation for the lower association with pain compared to OA and RA. For all TMJD subtypes, retrodiscal tissue vasculature was mainly innervated by sympathetic and unmyelinated sensory nerves. These findings enhance understanding of the neural basis of TMJD-related pain.

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Alfaro, J. J., Hovhannisyan, A. H., Locke, E. E., Amarista, F. J., Perez, D. E., Akopian, A. N.. 2025-06-15. Innervation of Retrodiscal Tissues in Patients with Temporomandibular Joint Disorder. https://doi.org/10.1101/2025.06.11.659119

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