Oral diseases, mainly encompassing dental caries and periodontal disease, are a significant public health concern affecting over 3.5 billion people worldwide (1). Oral pain (OP) is one of the most common and debilitating symptoms of oral diseases, characterized by an unpleasant sensory and emotional experience associated with actual or potential tissue damage (2). A study in the US based on the 2015–2018 National Health and Nutrition and Examination Survey (NHANES) showed that one out of four adults had OP, and 4% reported oral health-related productivity loss in the past year (3). OP is associated with a range of adverse psychosocial outcomes, including increased depression and anxiety and decreased quality of life (4). In addition, OP is a leading cause of reduced productivity, with the odds for oral health-related productivity loss being 13.85 times higher among individuals with OP (3). Furthermore, OP imposes a significant burden on the healthcare system, leading to increased medical costs related to consultation and treatment (5).

The etiology of OP is multifactorial, encompassing a variety of genetic, physiological, psychological, and environmental factors (6, 7). Among these factors, inflammation has emerged as a critical underlying mechanism in the development and persistence of OP (8, 9). Evidence suggests that oxidative stress can induce inflammasome activation, leading to subsequent release of inflammatory cytokines such as interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), which play a crucial role in the exacerbation of neuropathic OP⁷. Increasing evidence also suggests that diet plays a pivotal role in modulating systemic inflammation and thus is a potential modifiable risk factor of OP (10, 11). Studies show that certain dietary constituents that contain polyphenol compounds, carotenoids, and fatty acids may attenuate noxious sensory information by relieving nociceptive and/or pathological pain (10). Araújo et al. (11) conducted a randomized controlled trial (RCT) to test the effectiveness of a four-week gluten-free diet intervention among women with myofascial pain. Compared to the control group, the experiment group showed a significant reduction in pain intensity and an increase in pressure pain threshold (PPT), indicating the potential of diet therapy as an important alternative treatment plan for OP (11).

To improve the specificity of dietary scores, Shivappa et al. (12) developed the dietary inflammatory index (DII) to evaluate an individual’s dietary inflammatory potential according to the pro- and anti-inflammatory properties of various dietary components. DII is a comprehensive tool for diet quality and estimates the inflammation effects of dietary consumption of 45 nutrients associated with six inflammatory biomarkers: IL-1β, IL-4, IL-6, IL-10, TNF-α, and CRP (13, 14). DII is widely used to explore the relationship between diet and disease outcomes mediated through inflammation-related pathways (12). Previous studies reported that higher DII was associated with increased risks of metabolic disease (15), kidney disease (16), dementia (17), joint pain (18), headache (19), and mortality of all non-communicable diseases (20). Furthermore, accumulating evidence has also demonstrated positive associations between DII and several oral diseases, including oral cancer (21), periodontitis (22, 23), and gingivitis (24). These findings emphasize the essential role that DII plays in disease treatment and prevention.

However, little is known about the association between DII and OP in adults. To address the research gap, we conducted a cross-sectional study to explore the association between DII and OP based on a national sample from the NHANES database from 2003 to 2018. The findings may contribute to a deeper understanding of how diet-related inflammation correlates with OP, potentially guiding future longitudinal research that could inform dietary recommendations for OP management.

Our work may be the first study to find a U-shaped association between DII and OP using data from large-scale US adults based on NHANES. In this cross-sectional study based on a US population, we explored the relationship between DII and OP. A positive association was found, which persisted after testing for linear trends and adjusting for demographic data, lifestyle habits, BMI, and common comorbidities. After smoothing the curve, we found that this positive association was U-shaped, with 0.9479 being the significant turning point. Further subgroup analyses indicated no significant differences across different stratifications.

Our study showed that participants’ demographic and clinical characteristics varied by OP status and DII quartile. Participants in the OP group had significantly higher DII scores, indicating a more pro-inflammatory diet. When examining DII in quartiles, we observed a significant trend, with the highest quartile (Q4) showing the greatest risk of OP. This trend was consistent across different age groups and sexes, although the interaction terms were not statistically significant. Our findings are consistent with previous studies showing a positive association between dietary inflammation and OP (21, 29). For instance, one study showed that participants with higher DII scores reported a higher degree of “Shanghuo,” which is a traditional concept characterized by “redness, swelling, fever and pain” in Traditional Chinese Medicine (29). Additionally, Luo et al. found that the inflammatory potential of diet, as measured by DII, was associated with an increased risk of oral cancer, suggesting a broader impact of diet on oral health beyond pain alone (21). However, our study is unique in identifying a U-shaped relationship, indicating that both excessively high and low inflammatory diets can increase the risk of OP. This nuance has not been extensively documented in the context of oral health.

The U-shaped relationship between the DII and OP observed in our study might be attributed to several intertwined biological mechanisms. High DII scores, indicative of diets rich in pro-inflammatory foods (e.g., refined carbohydrates, red meats, and sugary beverages), are associated with increased levels of inflammatory markers such as CRP, IL-6, and TNF-α (13, 14). These cytokines play crucial roles in inflammation and pain by promoting leukocyte infiltration and macrophage accumulation, which activates pain pathways and exacerbates pain perception (13). Pro-inflammatory diets also elevate oxidative stress by increasing the production of reactive oxygen species (ROS). These ROS can damage cellular structures, including lipids, proteins, and DNA, leading to further inflammation and pain, particularly in sensitive tissues such as the oral mucosa and periodontal tissues (8). High DII diets may influence the gut microbiome composition, promoting the growth of pathogenic bacteria that produce pro-inflammatory metabolites (30). These metabolites can enter systemic circulation and exacerbate inflammation, impacting local oral health through the gut-oral axis (31, 32).

Low DII scores may reflect a deficiency in anti-inflammatory nutrients such as vitamins A, C, D, E, selenium, and omega-3 fatty acids. Diets low in anti-inflammatory nutrients can disrupt hormonal balance, affecting pain perception. Nutritional deficiencies can impair the immune system’s ability to control inflammation effectively (33). Micronutrients can regulate gene transcription factors, such as the proinflammatory nuclear factor kappa B and the anti-inflammatory nuclear factor (erythroid-derived 2)-like 2 (34). A lack of essential vitamins and minerals weakens the body’s antioxidant defenses, increasing oxidative stress and inflammation, thus heightening pain sensitivity (35). For example, omega-3 fatty acids have anti-inflammatory properties that mitigate OP by inhibiting the production of pro-inflammatory eicosanoids (36, 37). Deficiencies in vitamin D and omega-3 fatty acids have been linked to dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which is crucial for pain modulation (38–40).

Our findings suggest that maintaining a balanced diet that avoids extremes of the DII spectrum may help manage OP. Clinicians should consider dietary counseling as part of a comprehensive pain management strategy for patients with OP. Emphasizing a diet rich in anti-inflammatory foods while avoiding excessive intake of pro-inflammatory foods could be beneficial. Additionally, our stratified analysis indicates that females might particularly benefit from dietary modifications due to the stronger association between DII and OP in females. Tailoring dietary recommendations to individual patient characteristics, such as sex and specific inflammatory profiles, may enhance the effectiveness of dietary interventions for managing OP.

There are some limitations of this study. First, the present results should be interpreted with caution, as cross-sectional observational studies cannot demonstrate causation and directionality. Second, although confounding factors have been extensively adjusted, there may be other confounders that have not been included and adjusted. Third, Data were based on a self-reported questionnaire, which may be subject to recall bias, particularly concerning OP. Additionally, due to the limitations in the food composition data available in NHANES, we were unable to include plant-based compounds with antioxidant properties in the DII calculation, which may introduce some bias in the results. Future longitudinal study designs with more objective measurement of key variables and controlling for more confounders are needed.

This study provides evidence supporting the U-shape association between DII and OP, suggesting that maintaining a balanced diet that avoids extremes of the DII spectrum may help manage OP. These findings underscore the importance of dietary interventions in the management and prevention of OP. It is necessary to further study the relationship between DII and OP to determine the specific mechanism of DII on OP.