Chemotherapy-Induced Peripheral Neuropathy Impairs Tertiary Dentine Formation: An In Vivo Study

Abstract

Introduction and aims

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.

Methods

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.

Results

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.

Conclusion

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.

Clinical Relevance

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.