Biology subjects

Alfaro, J. J.

Publications and source records attributed to Alfaro, J. J..

3 recordsLinked to original sources

bioRxiv2025

Innervation of Retrodiscal Tissues in Patients with Temporomandibular Joint Disorder

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.

neuroscience↗

bioRxiv2025

Identification of Sensory Fiber Types in Mouse Temporomandibular Joint Tissues

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.

neuroscience↗

bioRxiv2025

Modeling Masticatory Myalgia to Headache-like Referred Pain Triggers Local Gene Plasticity at Referred Pain Sites

Patients with myofascial pain in the head and neck area report widespread and referred pain, including headache. Existing preclinical models fail to replicate this clinical phenotype; therefore, we aimed to develop animal models mimicking referred pain phenomenon and investigate whether referred pain leads to gene plasticity at the referred sites. We modeled masticatory myalgia by stimulation of either the masseter (MM) or temporal muscle (TM) in mice. MM and TM were stimulated with a single high-dose injection of Collagenase-type II (Col), repetitive low-dose Col injections, repetitive gentle MM stimulation, or single or repetitive forceful mouth opening. Referred pain was assessed by measuring mechanical hypersensitivity in the periorbital area (representing headache-like behavior) and another masticatory muscle. Stimulation of the MM, whether through single or repetitive Col injections or mouth opening, produced inconsistent, short-lasting (1-2 days) headache-like behavior in both males and females. In contrast, stimulation of the TM, using different paradigms, triggered mechanical hypersensitivity in both the MM and the periorbital area. Referred headache-like behavior lasted longer in females compared to males, while referred myalgia in the MM was pronouncer in males. The referred pain in the MM and periorbital areas triggered by TM stimulation was associated with significant gene plasticity in the MM and dura mater. Transcriptional changes in the MM following Col injection into the TM resembled those observed after direct MM injections. Presented data imply that referred pain modeled by TM stimulation could be accounted by nociceptive signaling from multiple local sites involved in this referred pain network.

neuroscience↗