Effects of ovariectomy of rat on tongue neuropathy: Revealing the crucial pathogenesis of burning mouth syndrome

We read with great interest the recent article by Kobayashi M et al., titled “Effects of ovariectomy of rat on tongue neuropathy: Relevance to burning mouth syndrome.”1 The study features a rigorous experimental design and comprehensive data. It successfully demonstrates the intrinsic link between estrogen deficiency and reduced tongue nerve fiber density, alongside the upregulation of transient receptor potential vanilloid 1 (TRPV1) expression. These findings provide crucial experimental evidence for the neuropathological mechanisms of burning mouth syndrome (BMS), with significant academic value and clinical implications. To further deepen the interpretation of these findings and inform subsequent research, the following three points are proposed for discussion.

First, the study utilized 9-week-old female Sprague–Dawley rats, whose physiological developmental stage roughly corresponds to human adolescence. However, clinically, BMS primarily affects middle-aged and older women, particularly those in the perimenopausal period. Hormonal fluctuations during this phase, particularly declining estrogen levels, are considered a significant risk factor. Future studies may consider employing 16–18-week-old female rats to construct models,2 as ovarian function in this age group begins to naturally decline, with hormonal fluctuations more closely resembling the endocrine characteristics of human perimenopause. Furthermore, if exogenous estrogen supplementation in ovariectomized rat models were shown to restore pain behavior or neurosensitivity indicators to levels comparable to those observed in sham-operated controls, this would provide direct evidence supporting the central role of estrogen deficiency in the pathogenesis of BMS. Such findings could offer an experimental rationale for hormone replacement therapy.

Second, pathological sections were obtained from a site 1 cm posterior to the tongue tip, primarily encompassing fungiform and filiform papillae. Although the tongue is the most common site of onset, many patients report symptoms originating from the palate and lips.3 Notably, neither of these sites contains papillary structures, and their neural innervation characteristics may differ significantly from those of the tongue. Future studies should specifically analyze tissue samples collected from the palate and lips. Immunohistochemical assessment and comparative analysis of nerve fiber density and TRPV1 expression in these regions could more accurately and comprehensively characterize the neuropathological features of the lesion sites, thereby aligning research findings with clinical pathological characteristics.

Third, we highly commend the authors’ use of ovariectomized rats to establish the BMS model, which directly mirrors the female-predominant clinical epidemiology of BMS. Although male patients with BMS exhibit lower clinical incidence, this population should not be overlooked.4 Further studies should determine whether sex hormone imbalance plays a similar role in males and incorporate a castrated male rat control group to investigate the potential role of androgens in regulating lingual nerve sensitivity. This would comprehensively elucidate the bidirectional regulatory mechanisms of sex hormones in BMS pathogenesis.

In conclusion, we sincerely thank this team for their outstanding contributions to basic BMS research. We look forward to their continued production of high-quality research and collaboration with oral and maxillofacial researchers worldwide. Such efforts are essential to advancing scientific understanding and achieving clinical breakthroughs for this intractable disease, which is a shared mission uniting our field.