Alshanqiti Ishraq, Son Hyeonwi, Shannonhouse John, Hu Jiaxin, Kumari Sinu, Parastooei Ghazaal, Raman Swarnalakshmi, Wang Sheng, Ro Jin Y, Kim Yu Shin, Chung Man-Kyo
Program in Dental Biomedical Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, United States.
Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, United States.
Pain. 2024 Dec 17;166(7):1597-1609. doi: 10.1097/j.pain.0000000000003498.
Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. Recent studies have suggested that external or intrinsic trauma to the temporomandibular joint (TMJ) is associated with the onset of painful TMD in patients. Here, we investigated the effects of TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors in both sexes. Forced-mouth opening increased mechanical pain as assessed by the von Frey test, with spontaneous pain-like behaviors assessed using the mouse grimace scale and anxiety-like behaviors assessed using the open-field test. Changes in pain-like behaviors were not different between male and female mice. However, in vivo GCaMP Ca 2+ imaging of intact trigeminal ganglia (TG) showed modality- and sex-dependent changes. Forced-mouth opening increased spontaneous Ca 2+ responses and mechanical hypersensitivity of TG neurons compared to the sham group, which was more pronounced in male mice. Forced-mouth opening also increased Ca 2+ responses evoked by cold, heat, and capsaicin stimuli, which was not different between the sexes. In retrogradely labeled trigeminal TMJ afferents, FMO induced an increase in small-sized neuronal proportions with increased colocalization with calcitonin gene-related peptides and transient receptor potential vanilloid subtype 1, which was modestly sex dependent. These results suggest that TMJ injury leads to persistent posttraumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors with distinct sex dependency.
颞下颌关节紊乱病（TMD）是颅面部最常见的疼痛性疾病。最近的研究表明，颞下颌关节（TMJ）的外部或内在创伤与患者疼痛性TMD的发作有关。在此，我们通过强迫张口（FMO）研究了TMJ创伤对小鼠的影响，以确定两性三叉神经伤害感受器的疼痛行为和外周敏化。通过von Frey试验评估，强迫张口增加了机械性疼痛，使用小鼠 grimace量表评估自发疼痛样行为，使用旷场试验评估焦虑样行为。雄性和雌性小鼠的疼痛样行为变化没有差异。然而，完整三叉神经节（TG）的体内GCaMP Ca²⁺成像显示了与模式和性别相关的变化。与假手术组相比，强迫张口增加了TG神经元的自发Ca²⁺反应和机械性超敏反应，这在雄性小鼠中更为明显。强迫张口还增加了冷、热和辣椒素刺激诱发的Ca²⁺反应，两性之间没有差异。在逆行标记的三叉神经TMJ传入纤维中，FMO诱导小尺寸神经元比例增加，与降钙素基因相关肽和瞬时受体电位香草酸亚型1的共定位增加，这有适度的性别依赖性。这些结果表明，TMJ损伤导致与三叉神经伤害感受器外周敏化相关的持续性创伤后痛觉过敏，且具有明显的性别依赖性。
