Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome Giuseppe Lauria a,*, Alessandra Majorana b, Monica Borgna a, Raffaella Lombardia, Paola Penza a, Alessandro Padovani c, Pierluigi Sapelli b a Immunology and Muscular Pathology Unit, National Neurological Institute ‘Carlo Besta’, Via Celoria, 11, 20133 Milan, Italy b Dental Clinic, School of Dentistry, University of Brescia, Brescia, Italy c Neurological Clinic, University of Brescia, Brescia, Italy Received 14 October 2004; received in revised form 15 February 2005; accepted 11 March 2005 Abstract Burning mouth syndrome is a common disorder that frequently affects women in the 5th–7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two-thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co-localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub-papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small-fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients. Pain 115 (2005) 332–337 Published by Elsevier B.V.