Burning mouth syndrome (BMS) is characterized by chronic burning pain in a normal-appearing oral mucosa. An important implication regarding the mechanism of pathogenesis is that the disease generally develops in postmenopausal women. I read with great interest the paper by Seol et al. on the regulation of transient receptor potential vanilloid 1 (TRPV1) as an estrogen-dependent nociceptor in BMS patients.1 They argued that estrogen has both pro-nociceptive and anti-nociceptive effects via modulation of nociceptors. Estrogen upregulates TRPV1 through classical genomic and non-classical pathways, resulting in pro-nociceptive effect. On the other hand, estrogen alleviates pain by downregulating nerve growth factor (NGF), which can translocate TRPV1 to the cell surface membrane.
How do the opposing effects of estrogen on pain perception affect the development of BMS? As a first hit by estrogen, increased estrogen during puberty increases TRPV1 expression, making at-risk individuals more sensitive to pain and more pain induced by dental treatment. In fact, BMS patients may have migraine headaches related to TRIPV1 and neuroinflammation prior to the onset of BMS.2 As a second hit by estrogen, when estrogen decreases during menopause, NGF increases, TRPV1 increases at the cell surface, pain sensitivity increases, neuroinflammation also occurs, and BMS develops in at-risk individuals. In fact, TRPV1 expression is increased in the oral mucosa of BMS patients.3 Two-hit by estrogen may explain gender differences in BMS patients. However, future studies on changes in estrogen and TRPV1 expression and rigorous investigation of pre-existing painful conditions in BMS patients are needed to validate this.
Declaration of competing interest
The author has no conflicts of interest relevant to this article.
Acknowledgments
This study has no source of fundings.
References
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