Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80131 Naples, Italy.
Int J Mol Sci. 2024 Oct 24;25(21):11442. doi: 10.3390/ijms252111442.
Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder, characterized by persistent burning sensations and pain without clear pathological causes. Recent research suggests that small fiber neuropathy (SFN) may play a significant role in the neuropathic pain and sensory disturbances associated with BMS. Following PRISMA guidelines, this systematic review aims to evaluate and synthesize current evidence supporting SFN's involvement in BMS. The protocol is registered in PROSPERO (CRD42024555839). The results show eight studies reported reductions in nerve fiber density in tongue biopsies (ranging from 30% to 60%), along with morphological changes indicative of small fiber damage. Additionally, an increase in TRPV1-positive, NGF-positive, and P2X3-positive fibers, overexpression of Nav1.7, and slight underexpression of Nav1.9 mRNA were observed in BMS patients. Quantitative Sensory Testing in seven studies revealed sensory abnormalities such as reduced cool detection and cold pain thresholds. Blink reflex and corneal confocal microscopy also indicated peripheral and central small fiber damage, along with increased artemin mRNA expression. The evidence strongly supports SFN as a key factor in the pathophysiology of BMS, particularly due to reductions in nerve fiber density and altered sensory thresholds. However, variability across studies highlights the need for larger, standardized research to establish causal relationships and guide therapeutic strategies.
灼口综合征（BMS）是一种慢性特发性或口腔面部疼痛障碍，其特征为持续性烧灼感和疼痛，而无明确的病理原因。最近的研究表明，小纤维神经病（SFN）可能在与 BMS 相关的神经病理性疼痛和感觉障碍中起重要作用。根据 PRISMA 指南，本系统评价旨在评估和综合目前支持 SFN 参与 BMS 的证据。该方案已在 PROSPERO（CRD42024555839）中注册。结果表明，八项研究报告了舌活检中神经纤维密度降低（范围为 30%至 60%），以及小纤维损伤的形态学变化。此外，BMS 患者中 TRPV1 阳性、NGF 阳性和 P2X3 阳性纤维增加，Nav1.7 过度表达，Nav1.9mRNA 轻度表达不足。七项研究中的定量感觉测试显示出感觉异常，如冷觉检测和冷痛阈值降低。眨眼反射和角膜共聚焦显微镜也表明存在外周和中枢小纤维损伤，以及 artemin mRNA 表达增加。证据强烈支持 SFN 作为 BMS 病理生理学的关键因素，特别是由于神经纤维密度降低和感觉阈值改变。然而，研究之间的变异性突出表明需要更大、标准化的研究来确定因果关系并指导治疗策略。
