Chronic pain is the predominant symptom that drives temporomandibular joint osteoarthritis (TMJOA) patients to seek medical care; however, currently used treatment modalities remain less effective. This study aimed to investigate chronic pain and the peripheral and central responses in monoiodoacetate (MIA)-induced TMJOA rats. First, the appropriate dose of MIA was determined based on pain behavior assessment in rats. Alterations of the condylar structure in TMJOA rats were evaluated by histological staining and micro-computed tomography (micro-CT). Second, the period of TMJOA chronic pain was further explored by assessing the numbers of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium-binding adaptor molecule 1 (IBA-1)-positive microglia in the trigeminal spinal nucleus (TSN) and performing nonsteroidal anti-inflammatory drug (NSAID) efficacy experiments. Finally, the expression of neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4) in the trigeminal ganglion (TG) and TSN was assessed by immunofluorescence. MIA at 4 mg/kg was considered an appropriate dose. Gradual MIA-induced alterations of the condylar structure were correlated with temporomandibular joint (TMJ) pain. The numbers of GFAP- and IBA-1-positive cells were increased at 2, 3, and 4 weeks after MIA injection. NSAIDs failed to alleviate pain behavior 10 days after MIA injection. CGRP and IB4 levels in the TG and TSN were upregulated at 2 and 4 weeks. These results suggest that TMJOA-related chronic pain emerged 2 weeks after MIA injection. CGRP- and IB4-positive afferents in both the peripheral and central nervous systems may be involved in MIA-induced TMJOA-related chronic pain in rats.

慢性疼痛是促使颞下颌关节骨关节炎（TMJOA）患者就医的主要症状；然而，目前使用的治疗方式仍然不太有效。本研究旨在研究单碘乙酸 (MIA) 诱导的 TMJOA 大鼠的慢性疼痛以及外周和中枢反应。首先，根据大鼠的疼痛行为评估确定适当的 MIA 剂量。通过组织学染色和微型计算机断层扫描 (micro-CT) 评估 TMJOA 大鼠髁突结构的改变。第二，通过评估三叉脊髓核 (TSN) 中胶质纤维酸性蛋白 (GFAP) 阳性星形胶质细胞和离子化钙结合接头分子 1 (IBA-1) 阳性小胶质细胞的数量，进一步探索 TMJOA 慢性疼痛的时期，并进行非甾体抗炎药（NSAID）疗效实验。最后，通过免疫荧光评估三叉神经节 (TG) 和 TSN 中神经丝 200 (NF200)、降钙素基因相关肽 (CGRP) 和异凝素 B4 (IB4) 的表达。4 mg/kg 的 MIA 被认为是合适的剂量。逐渐 MIA 引起的髁突结构改变与颞下颌关节 (TMJ) 疼痛相关。在 MIA 注射后 2、3 和 4 周，GFAP 和 IBA-1 阳性细胞的数量增加。MIA 注射后 10 天，NSAID 未能缓解疼痛行为。TG 和 TSN 中的 CGRP 和 IB4 水平在第 2 周和第 4 周时上调。这些结果表明 TMJOA 相关的慢性疼痛在 MIA 注射后 2 周出现。外周和中枢神经系统中的 CGRP 和 IB4 阳性传入神经可能参与 MIA 诱导的大鼠 TMJOA 相关慢性疼痛。