Journal Article

Effects of topically applied liquid N-acetylcysteine for the management of burning mouth syndrome

Kim, Choung-Soo, Lee, Dong Won, Kim, Ji Won, Cho, Kwang-Jae, Won, Ho-Ryun, Choi, Jeong-Seok, Kwon, Minsu, Joo, Young-Hoon, Woo, Seung Hoon, Koo, Bon Seok

2025

Overview

Burning Mouth Syndrome (BMS) is a chronic neuropathic pain condition with limited treatment options. N-acetylcysteine (NAC), a thiol-based antioxidant with neuroprotective properties, has not been clinically evaluated as a topical agent for BMS. This study aimed to evaluate the efficacy of topically applied liquid NAC in reducing symptoms and improving quality of life of patients with BMS. In a multicenter, prospective, nonrandomized, open-label study, 114 patients with BMS were allocated to receive liquid NAC oral rinse, oral clonazepam, or combination therapy for eight weeks. Symptoms were assessed at baseline, week 4, and week 8 using the visual analog scale (VAS) and the Korean version of the Oral Health Impact Profile-14 (OHIP-14 K). Across all three groups, VAS scores declined significantly within groups from baseline to week 4 and to week 8; however, the magnitude of VAS change did not differ between groups at either time point. For OHIP‑14 K, significant within‑group decreases were observed in the liquid NAC and combination groups from baseline to weeks 4 and 8, whereas the clonazepam group showed a significant decrease only from week 4 to week 8 and not from baseline. At week 4, the combination group achieved a larger OHIP‑14 K reduction than either monotherapy; by week 8, between‑group differences were no longer significant. Topically applied liquid NAC, alone or in combination with clonazepam, effectively reduced pain and enhanced patient-reported outcomes. These findings support the potential of a localized and safe strategy targeting neuropathic mechanisms in BMS. Topically administered liquid NAC demonstrates potential as an effective and well-tolerated therapeutic strategy for managing BMS, offering symptom relief with minimal systemic burden. Although the combination with clonazepam did not demonstrate sustained superiority at 8 weeks, its principal advantage is a faster onset of improvement in OHIP‑14 K, evident by week 4.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/378 / 692/308 / 692/617 / 692/699 / 692/700 / Acetylcysteine / Acetylcysteine - administration & dosage / Acetylcysteine - therapeutic use / Administration, Topical / Adult / Aged / Analgesics / Burning mouth syndrome / Burning Mouth Syndrome - drug therapy / Chronic pain / Clonazepam / Clonazepam - administration & dosage / Clonazepam - therapeutic use / Combination therapy / Female / Humanities and Social Sciences / Humans / Likert scale / Liquid n-acetylcysteine / Male / Middle Aged / multidisciplinary / Neuralgia / Neuroprotection / Oral health-related quality of life / Oral hygiene / Pain / Pain Measurement / Patients / Prospective Studies / Quality of Life / Science / Science (multidisciplinary) / Topical therapy / Treatment Outcome