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Immune and Endocrine Function in Patients With Burning Mouth Syndrome

Koike, Kazuyoshi DDS, PhD*,†; Shinozaki, Takahiro DDS*,†; Hara, Kazuhiko DDS*; Noma, Noboru DDS, PhD*,†; Okada-Ogawa, Akiko DDS, PhD*,†; Asano, Masatake DDS, PhD†,‡; Shinoda, Masamichi DDS, PhD†,§; Eliav, Eli DMD, DDS, PhD; Gracely, Richard H. PhD; Iwata, Koichi DDS, PhD†,§; Imamura, Yoshiki DDS, PhD*,†

doi: 10.1097/AJP.0b013e31828c4bf1
Original Articles

Objectives: Research suggests that varied etiologic factors are responsible for burning mouth syndrome (BMS). We examined the role of immune and endocrine function in the pathology of BMS.

Methods: We conducted a case-control study to evaluate immune (lymphocyte subpopulations) and endocrine (hypothalamus-pituitary-adrenal axis and sympathetic-adrenomedullary system) function in 47 female BMS patients and 47 age-matched female controls presenting at an university clinic. Psychological state was assessed with the Zung Self-Rating Depression Scale and Taylor Manifest Anxiety Scale.

Results: BMS patients were significantly more anxious than controls (P=0.011). Plasma adrenaline level was significantly lower (P=0.020) in BMS patients than in controls, and linear regression analysis of all patients combined revealed that depression level was significantly positively associated with plasma noradrenaline and cortisol levels (P=0.002 and 0.001, respectively). However, as compared with controls, BMS patients had a significantly lower CD8(+) cell count (P<0.001) and a significantly higher CD4/CD8 ratio (P=0.002). Discriminant analysis revealed that CD8(+) cell count and CD4/CD8 ratio were independent variables that distinguished BMS patients from controls.

Discussion: The immunoendocrine system is substantially involved, and may have a key role, in the mechanism of chronic pain in BMS patients. Immune function was significantly and specifically suppressed in BMS, although the hypothalamic-pituitary-adrenal axis and sympathetic nervous system were predominantly activated by psychological stress that was not specific to BMS.

Departments of *Oral Diagnostic Sciences


§Physiology, Nihon University School of Dentistry

Division of Clinical Research, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan

Department of Diagnostic Sciences, Division of Orofacial Pain, University of Medicine and Dentistry, New Jersey Dental School, Newark, NJ

Center for Neurosensory Disorders, University of North Carolina School of Dentistry, Chapel Hill, NC

The authors declare no conflict of interest. Supported in part by Grants-in-Aid for Scientific Research to Y.I.; Nihon University Multidisciplinary Research Grants for 2010, 2011, and 2012 to Y.I, K.I., and M.S.; a Sato Fund Research Grant to Y.I.; and Grants from the Dental Research Center, Nihon University School of Dentistry to Y.I. R.G. formerly received honoraria from Eli Lilly Pharm. (Indianapolis, IN), Jazz Pharm. (Philadelphia, PA), Abbot Pharm. (Abbott Park, IL), Wyeth Pharm. (Overland Park, KS), and D C Rheumatological Society and currently owns stock in Algynomics Inc (Chapel Hill, NC).

Reprints: Yoshiki Imamura, DDS, PhD, Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Kandasurugadai 1-8-13, Chiyoda-ku, Tokyo 101-8310, Japan (e-mail:

Received February 7, 2012

Accepted February 7, 2013

© 2014 by Lippincott Williams & Wilkins