Small Fiber Neuropathy in Burning Mouth Syndrome: A Systematic Review

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.

• Publication year

  2024

• Venue

  International Journal of Molecular Sciences

• Publication date

  2024-10-24

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/ijms252111442PMID 39518993PMCID 11546372
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Cutaneous nerve biopsy in patients with symptoms of small fiber neuropathy: a retrospective study

  2024cited by this paper
• Neuropsychological assessment of Romanian burning mouth syndrome patients: stress, depression, sleep disturbance, and verbal fluency impairments

  2023cited by this paper
• Burning mouth syndrome: Analysis of diagnostic delay in 500 patients.

  2023cited by this paper
• Voltage-gated sodium channels gene expression in Burning Mouth Syndrome: a case-control study.

  2023cited by this paper
• Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy

  2022cited by this paper
• White matter hyperintensities in Burning Mouth Syndrome assessed according to the Age-Related White Matter Changes scale

  2022cited by this paper
• CPC07: Erythromelalgia associated with small‐fibre neuropathy

  2022cited by this paper
• The use of self‐report questionnaires in an analysis of the multidimensional aspects of pain and a correlation with the psychological profile and quality of life in patients with burning mouth syndrome: A case‐control study

  2022cited by this paper
• Small fiber neuropathy: Swiss cohort characterization

  2021cited by this paper
• Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability

  2021influential reference
• Burning Fog: Cognitive Impairment in Burning Mouth Syndrome

  2021cited by this paper
• A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy.

  2021cited by this paper
• Worldwide Prevalence Estimates of Burning Mouth Syndrome: A Systematic Review and Meta-analysis.

  2021influential reference
• Psychophysical characterization of burning mouth syndrome - A systematic review and meta-analysis.

  2020influential reference
• International Classification of Orofacial Pain, 1st edition (ICOP)

  2020cited by this paper
• Characterization of Models for Identifying Physical and Cognitive Frailty in Older Adults With Diabetes: Systematic Review and Meta-Analysis

  2020cited by this paper
• Differences in personality, perceived stress and physical activity in women with burning mouth syndrome compared to controls

  2020cited by this paper
• Diagnostic criteria for idiopathic small fiber neuropathy: A systematic review

  2020cited by this paper
• Current View of Diagnosing Small Fiber Neuropathy

  2020cited by this paper
• Clinical diagnosis and management of small fiber neuropathy: an update on best practice

  2020cited by this paper
• Neurophysiology and genetics of burning mouth syndrome

  2019influential reference
• Differential Diagnosis of Chronic Neuropathic Orofacial Pain: Role of Clinical Neurophysiology.

  2019cited by this paper
• Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review.

  2019cited by this paper
• Assessment of Oral Health-related Quality of Life, measured by OHIP-14 and GOHAI, and psychological profiling in Burning Mouth Syndrome: a case-control clinical study.

  2019cited by this paper
• Corneal Confocal Microscopy Detects Small-Fiber Neuropathy in Burning Mouth Syndrome: A Cross-Sectional Study.

  2019cited by this paper
• Small‐fiber neuropathy: Expanding the clinical pain universe

  2019cited by this paper
• Erythromelalgia: a cutaneous manifestation of neuropathy?

  2018cited by this paper
• Fibromyalgia and small‐fiber polyneuropathy: What's in a name?

  2018cited by this paper
• Burning mouth syndrome: a diagnostic challenge.

  2018cited by this paper
• The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes.

  2017cited by this paper
• Small fibre neuropathy

  2017cited by this paper
• Understand spiciness: mechanism of TRPV1 channel activation by capsaicin

  2017cited by this paper
• Profiling intraoral neuropathic disturbances following lingual nerve injury and in burning mouth syndrome

  2017influential reference
• Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders.

  2017cited by this paper
• Small fiber neuropathy: Diagnosis, causes, and treatment.

  2017cited by this paper
• Associated conditions in small fiber neuropathy – a large cohort study and review of the literature

  2017cited by this paper
• The Detection of Small-Fiber Neuropathies in Burning Mouth Syndrome and Iatrogenic Lingual Nerve Injuries: Use of Quantitative Sensory Testing.

  2016influential reference
• Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

  2016cited by this paper
• Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

  2016influential reference
• Advances in diagnostics and outcome measures in peripheral neuropathies.

  2015influential reference
• Thermal and mechanical quantitative sensory testing in chinese patients with burning mouth syndrome – a probable neuropathic pain condition?

  2015influential reference
• Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.

  2015cited by this paper
• Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome

  2015influential reference
• Burning mouth syndrome: A review on its diagnostic and therapeutic approach

  2014cited by this paper
• Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis.

  2014cited by this paper
• The clinical approach to small fibre neuropathy and painful channelopathy

  2014cited by this paper
• Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.

  2014cited by this paper
• Idiopathic Small Fiber Neuropathy: Phenotype, Etiologies, and the Search for Fabry Disease

  2014cited by this paper
• Corneal innervation as a window to peripheral neuropathies.

  2013cited by this paper
• Incidence and prevalence of small-fiber neuropathy

  2013cited by this paper
• Evaluation of select neurophysiological, clinical and psychological tests for burning mouth syndrome.

  2012cited by this paper
• Pathophysiology of primary burning mouth syndrome.

  2012cited by this paper
• Gain-of-function Nav1.8 mutations in painful neuropathy

  2012cited by this paper
• Pathophysiology of Langerhans cells

  2012cited by this paper
• Diagnosis and Treatment of Pain in Small-fiber Neuropathy

  2011cited by this paper
• Thermal sensory and pain thresholds in the tongue and chin change with age, but are not altered in burning mouth syndrome

  2011cited by this paper
• Sensory purinergic receptor P2X3 is elevated in burning mouth syndrome.

  2010cited by this paper
• “Burning Tongue” and “Burning Tip”: The Diagnostic Challenge of the Burning Mouth Syndrome

  2010influential reference
• Corneal Confocal Microscopy

  2010cited by this paper
• Enhanced Artemin/GFRα3 Levels Regulate Mechanically Insensitive, Heat-Sensitive C-Fiber Recruitment after Axotomy and Regeneration

  2010cited by this paper
• Pain as a channelopathy.

  2010cited by this paper
• Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

  2010cited by this paper
• Assessment of oral trigeminal sensitivity in humans

  2007influential reference
• Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score.

  2007influential reference
• Sodium channel blockade may contribute to the analgesic efficacy of antidepressants.

  2007cited by this paper
• GDNF family receptor complexes are emerging drug targets.

  2007cited by this paper
• Small-fiber neuropathy: answering the burning questions.

  2006cited by this paper
• Artemin Overexpression in Skin Enhances Expression of TRPV1 and TRPA1 in Cutaneous Sensory Neurons and Leads to Behavioral Sensitivity to Heat and Cold

  2006cited by this paper
• Trigeminal small‐fiber sensory neuropathy causes burning mouth syndrome

  2005influential reference
• Striatal dopamine D1 and D2 receptors in burning mouth syndrome

  2003cited by this paper
• Quantitative sensation testing in small‐diameter sensory fiber neuropathy

  2002cited by this paper
• Pain threshold and pain recovery after experimental stimulation in patients with burning mouth syndrome

  2002influential reference
• Small‐fiber neuropathy

  2002cited by this paper
• Small-fiber dysfunction in trigeminal neuralgia

  2001cited by this paper
• Pharmacologic treatment of pain in polyneuropathy

  2000cited by this paper
• Sensory and pain thresholds to orofacial argon laser stimulation in patients with chronic burning mouth syndrome.

  1993influential reference
• Clinical features of burning mouth syndrome.

  1987influential reference
• Afferent impulses in cutaneous sensory nerves in human subjects.

  1960cited by this paper

• Burning Mouth Syndrome as a Central Pain Disorder: A Case Study Demonstrating Response to Occipital Nerve Block Treatment.

  2026cites this paper
• The Role of Stress in Burning Mouth Syndrome Triggered by Dental Treatments: A Two‐Step Hypothesis

  2025cites this paper
• Potential Target Receptors for the Pharmacotherapy of Burning Mouth Syndrome

  2025cites this paper
• Looking at Burning Mouth Syndrome Brain: The Prevalence of Idiopathic Intracranial Hypertension Radiologic Signs in BMS Patients

  2025cites this paper
• Managing Burning Mouth Syndrome: Current and Future Directions

  2025cites this paper
• Morpho‐Histo‐Cytological Evaluation of Oral Tissues in Burning Mouth Syndrome: A Systematic Review

  2025influential citation
• Evaluating Large Language Models for Burning Mouth Syndrome Diagnosis

  2025cites this paper
• Burning Mouth Syndrome: A Neurological Reappraisal Through Idiopathic Intracranial Hypertension and Glymphatic Dysfunction.

  2025cites this paper
• Burning Mouth Syndrome: Unraveling Multifactorial Etiologies and Advancing Management Strategies.

  2025cites this paper
• Beyond Osteoarthritis: Emerging Applications of Anti-NGF Monoclonal Antibodies in Pain Management in Dogs and Cats

  2025cites this paper
• A Pharmacological and Critical Review of Caffeine and Alpha-Lipoic Acid for Burning Mouth Syndrome.

  2025cites this paper
• Age, Sex, and Neuroinflammation: A Unified Mechanism for Burning Mouth Syndrome Driven by Small Fiber Neuropathy and Central Sensitization.

  2025cites this paper
• Rethinking Burning Mouth Syndrome: A Nociplastic Pain Disorder Shaped by Sexual Dimorphism.

  2025cites this paper
• Pathophysiology of Burning Mouth Syndrome as a Neuropathic Disorder

  2024cites this paper