He Jun, Zhan Chaoning, Lu Yanli, Chen Junyang, Yang Xiaojun, Hou Jin
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Int Dent J. 2025 Jul 11;75(5):100899. doi: 10.1016/j.identj.2025.100899.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and well-documented adverse effect of chemotherapy, primarily targeting sensory nerves. Sensory nerves play a crucial role in the repair of dentine-pulp complex injuries. Despite this, the influence of CIPN on the repair processes of the dentine-pulp complex remains largely unexplored. This study aims to investigate the effects of paclitaxel-induced CIPN on tertiary dentine formation following dental injury, offering new insights into the connection between chemotherapy and dental tissue regeneration.
Male C57BL/6J mice received paclitaxel (PTX, 35 mg/kg) intraperitoneally to model CIPN. Mechanical withdrawal threshold (MWT) was tested with Von Frey filaments, and intraepidermal nerve fiber (IENF) degeneration was assessed using immunofluorescence for CIPN validation. Dental pulp analyses included peripheral nerve fiber density, Calcitonin Gene-Related Peptide (CGRP) levels, and odontoblast apoptosis, evaluated via immunofluorescence and TUNEL staining. Effects on trigeminal neurons and neuropeptide production were analysed using immunofluorescence for activating transcription factor 3 (ATF3) and CGRP. Tertiary dentine formation was evaluated histologically using H&E staining and Masson's trichrome.
PTX treatment reduced paw mechanical stimulation thresholds. IENF density decreased by nearly 50% post-paclitaxel. CGRP-positive nerve fibers in the dental pulp were notably reduced in PTX-treated mice. Histology showed substantial reductions in tertiary dentine formation in the CIPN groups. PTX did not cause odontoblast apoptosis or damage trigeminal neurons but reduced CGRP in dental pulp nerve endings.
PTX impairs neuropeptide transport and release in dental sensory nerves, affecting tertiary dentine formation. These findings offer key insights into CIPN's neurotoxic effects, with implications for dental pulp repair and regeneration.
Paclitaxel-induced peripheral neuropathy reduces tertiary dentine formation following dental injury. These findings suggest that chemotherapy patients may face compromised dental repair, emphasising the need for tailored dental management and monitoring of oral health during cancer treatment.
化疗诱导的周围神经病变（CIPN）是化疗常见且有充分文献记载的不良反应，主要影响感觉神经。感觉神经在牙本质 - 牙髓复合体损伤修复中起关键作用。尽管如此，CIPN对牙本质 - 牙髓复合体修复过程的影响在很大程度上仍未得到探索。本研究旨在探讨紫杉醇诱导的CIPN对牙齿损伤后第三期牙本质形成的影响，为化疗与牙组织再生之间的联系提供新见解。
雄性C57BL/6J小鼠腹腔注射紫杉醇（PTX，35mg/kg）以建立CIPN模型。用von Frey细丝测试机械撤针阈值，并用免疫荧光评估表皮内神经纤维（IENF）变性以验证CIPN。牙髓分析包括通过免疫荧光和TUNEL染色评估外周神经纤维密度、降钙素基因相关肽（CGRP）水平和成牙本质细胞凋亡。使用免疫荧光检测激活转录因子3（ATF3）和CGRP分析对三叉神经元和神经肽产生的影响。用苏木精 - 伊红染色和马松三色染色组织学评估第三期牙本质形成。
PTX治疗降低了爪部机械刺激阈值。紫杉醇注射后IENF密度降低了近50%。PTX处理的小鼠牙髓中CGRP阳性神经纤维明显减少。组织学显示CIPN组第三期牙本质形成显著减少。PTX未引起成牙本质细胞凋亡或损伤三叉神经元，但降低了牙髓神经末梢中的CGRP。
PTX损害牙感觉神经中的神经肽运输和释放，影响第三期牙本质形成。这些发现为CIPN的神经毒性作用提供了关键见解，对牙髓修复和再生具有重要意义。
紫杉醇诱导的周围神经病变减少牙齿损伤后的第三期牙本质形成。这些发现表明化疗患者的牙齿修复可能受到影响，强调在癌症治疗期间需要针对性的牙齿管理和口腔健康监测。
