Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Oral & Maxillofacial Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
J Orthop Res. 2022 Feb;40(2):338-347. doi: 10.1002/jor.25048. Epub 2021 Apr 16.
Orofacial pain is among the most common chronic pain conditions and can result from temporomandibular disorders (TMDs) of the temporomandibular joint (TMJ). Matrix metalloproteinases (MMPs) drive degeneration of TMJ tissues and likely mediate pain in TMJ disorders given their role in nociception. However, few studies have assessed MMPs in the TMJ innervated tissues nor in the context of pain. This study defined the extent of MMP-1, MMP-9, and MMP-2 in TMJ tissues from patients undergoing total joint replacement (TJR) or arthroplasty discectomy for painful TMJ disorders. Protein expression was probed by Western blot in TMJ disc and capsular ligaments taken during TJR (n = 6) or discectomy (n = 3) for osteoarthritis or internal derangement in an IRB-approved study. Pro- and active MMP-1, active MMP-9, and pro- and active MMP-2 are detectable. MMP-1 and MMP-9 correlate positively to each other (Kendall's τ = 0.63; p = 0.01), strengthening the hypothesis that they are mechanistically related in regulatory cascades. Active MMP-1 and active MMP-9 correlate positively with self-reported pain scores (τ ≥ 0.51; p ≤ 0.04), suggesting their involvement in peripheral nociception. Overall, neither MMPs nor pain correlate with the functional vertical opening of the jaw. MMP-1 varies with the observed stage of degeneration during surgery (p = 0.04). Neither overall MMPs nor pain correlate with the overall magnetic resonance imaging scores, corroborating the longstanding, but confounding, clinical observation that pain and radiological evidence of joint damage are not always related. Clinical significance: These findings suggest that MMPs mediate pain in innervated soft tissues and may be targets for diagnosing disease stage and treatments in painful TMJ disorders.
口腔颌面部疼痛是最常见的慢性疼痛病症之一,可能由颞下颌关节(TMJ)的颞下颌关节紊乱(TMD)引起。基质金属蛋白酶(MMPs)驱动 TMJ 组织退化,并可能在 TMJ 疾病中介导疼痛,因为它们在伤害感受中发挥作用。然而,很少有研究评估过 TMJ 神经支配组织中的 MMPs,也没有在疼痛的背景下评估过。本研究定义了接受全关节置换术(TJR)或关节盘切除术的患者的 TMJ 组织中 MMP-1、MMP-9 和 MMP-2 的程度,这些患者因疼痛性 TMJ 疾病接受了 TJR(n=6)或关节盘切除术(n=3)。在一项经过 IRB 批准的研究中,通过 Western blot 检测了取自 TJR(n=6)或关节盘切除术(n=3)的 TMJ 盘和关节囊韧带中的蛋白表达,用于骨关节炎或内部紊乱。可检测到前体和活性 MMP-1、活性 MMP-9、前体和活性 MMP-2。MMP-1 和 MMP-9 彼此呈正相关(Kendall's τ=0.63;p=0.01),这加强了它们在调节级联中具有机械相关性的假设。活性 MMP-1 和活性 MMP-9 与自我报告的疼痛评分呈正相关(τ≥0.51;p≤0.04),表明它们参与了外周伤害感受。总体而言,MMPs 或疼痛与下颌的功能垂直开口均无相关性。MMP-1 随手术中观察到的退化阶段而变化(p=0.04)。总体 MMPs 或疼痛与整体磁共振成像评分均无相关性,这证实了长期以来但令人困惑的临床观察,即疼痛和关节损伤的放射学证据并不总是相关的。临床意义:这些发现表明 MMPs 在神经支配的软组织中介导疼痛,并且可能是诊断疼痛性 TMJ 疾病的疾病阶段和治疗方法的靶点。