Alfaro Jessie J, Hovhannisyan Anahit H, Locke Erin E, Amarista Felix J, Perez Daniel E, Akopian Armen N
bioRxiv. 2025 Jun 15:2025.06.11.659119. doi: 10.1101/2025.06.11.659119.
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 (α-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.
颞下颌关节(TMJ)紊乱症(TMJDs)是一组影响口面部区域的肌肉骨骼疾病,常伴有面部疼痛。了解TMJ结构,特别是盘后组织的感觉神经支配,对于确定TMJD的疼痛机制至关重要,因为要研究这些机制,我们必须首先确定TMJ的感觉神经元组成。然而,关于TMJ组织内神经类型的数据仍然有限。本研究检查了接受双侧TMJ置换术(TMJR)的骨关节炎(OA)、类风湿关节炎(RA)或髁突增生(CH)的TMJD患者盘后组织中的感觉神经和交感神经分布。使用针对特定神经标记物的免疫组织化学方法来可视化和量化神经亚型。与RA和OA相比,CH组织中pgp9.5感觉纤维的密度显著降低,而RA和OA的水平相似。在所有亚型中,无髓鞘(pgp9.5 /NFH )与有髓鞘(pgp9.5 /NFH )纤维的比例约为70:30。大多数感觉神经是CGRP (肽能),而一小部分是CGRP (非肽能),其中一些是小白蛋白阳性(PV )。盘后组织中存在有髓鞘和无髓鞘的肽能以及非肽能纤维。除感觉神经支配外,所有盘后组织均含有酪氨酸羟化酶阳性(TH )的交感神经纤维,主要支配血管(α-平滑肌肌动蛋白(α-SMA ))。这些血管也主要由无髓鞘感觉纤维支配,有髓鞘感觉神经的输入有限。总之,所有TMJD亚型具有相似的神经组成,但CH组织的感觉神经密度降低,这可能是其与疼痛的关联低于OA和RA的一个解释。对于所有TMJD亚型,盘后组织血管主要由交感神经和无髓鞘感觉神经支配。这些发现增进了对TMJD相关疼痛神经基础的理解。