Alfaro, J. J.; Akopian, A. N.

Temporomandibular joint (TMJ) disorders (TMJDs) are linked to heightened nerve sensitivity in TMJ tissues. To set the groundwork for investigating the mechanisms governing this increased responsiveness, this study aimed to identify the types of nerves in the retrodiscal tissue (retrodisc), anterior disc, and joint capsule of mouse TMJ using immunohistochemistry (IHC) and reporter mice. The pan-sensory neuronal marker pgp9.5 revealed no nerves in the articular disc but identified approximately 70% unmyelinated and 30% myelinated fibers in other TMJ tissues. Nearly all sensory fibers in the joint capsule and anterior disc were CGRP+ peptidergic fibers, while the retrodisc contained about 80% peptidergic fibers. Notably, CGRP-/NFH+ myelinated non-peptidergic nerves were absent, indicating the absence of non-nociceptive fibers (A-LTMRs) in TMJ tissues. Almost all sensory fibers in the joint capsule and anterior disc were Htr3a+, with the retrodisc containing 60-70% Htr3a+ fibers. Additionally, TMJ tissues had minimal to no (<5%) MrgprD+, MrgprA3+, MrgprC11+, somatostatin+, or parvalbumin+ fibers, except for the retrodisc, which had about 20% Mrgpr+ fibers. Excluding articular discs, TMJ tissues were highly vascularized, with blood vessels surrounded by both sensory and sympathetic (TH+) nerves. Overall, TMJ tissues were predominantly innervated by peptidergic fibers, with a minor presence of other non-peptidergic nociceptors.