Abstract A high-sugar diet (HSD) is associated with various health issues, including metabolic dysfunction, inflammation, hypertension, and increased pain sensitivity. However, the metabolic pathways potentially involved in these processes remain incompletely understood. This exploratory metabolomic profiling study aimed to investigate HSD-related alterations in serum and salivary metabolites and to identify metabolic pathways potentially relevant to pain and blood pressure regulation. Rats were randomly divided into two groups: a control group receiving standard chow and regular water, and an HSD group fed a cariogenic diet supplemented with 5% sucrose water for 28 days. Serum and saliva samples were analyzed using liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based untargeted metabolomics. Metabolomic profiling and pathway analysis assessed metabolic changes regarding pain and blood pressure regulation. Significant differences were observed in the serum metabolite profiles between HSD and control groups. The HSD group showed alterations with 330 down-regulated and 72 up-regulated metabolites. Notably, metabolites associated with blood pressure regulation were impacted; up-regulated metabolites like lysophosphatidylcholine and midodrine were linked to increased blood pressure, while down-regulated metabolites like taurochenodeoxycholic acid and hypotaurine have been associated with antihypertensive effects. Additionally, metabolites linked to pain sensitivity, including N-arachidonoyl dopamine and acetaminophen glucuronide, were down-regulated. Pathway analysis identified 12 up-regulated pathways in HSD-fed rats, including starch and sucrose metabolism, associated with vascular dysfunction, and 14 down-regulated pathways, such as vitamin B6 and taurine metabolism, linked to cardiovascular protection. Salivary analysis showed 186 altered metabolites, particularly the down-regulation of the anti-inflammatory metabolite N-acetylanthranilic acid and the up-regulation of the antihypertensive agent bethanidine. Cross-biofluid analysis highlighted consistent changes in nucleotide and arginine/proline metabolism. This exploratory metabolomic profiling study demonstrated that HSD exposure was associated with broad metabolic alterations in serum and saliva. Several identified metabolites and pathways may be potentially relevant to biological processes involved in pain sensitivity and blood pressure regulation. These findings are hypothesis-generating and provide a foundation for future mechanistic and longitudinal studies investigating the metabolic effects of high-sugar diets.

OBJECTIVES:This study primarily investigated whether stimulated whole salivary (SWS) flow is correlated with minor salivary flow (MSF) in adults with xerostomia taking anticholinergic medications, and, secondarily, examined correlations between SWS and unstimulated whole salivary (UWS) flow and xerostomia severity. DESIGN:We conducted a cross-sectional study of 85 middle-aged adults (mean age: 57.1 ± 5.2 years, range: 45-64) taking anticholinergic medications. Salivary flow rates for SWS, UWS, and labial MSF were measured, and xerostomia severity was assessed using the Xerostomia Inventory (XI). Based on established cutoff values for SWS and UWS, participants were grouped into categories with or without UWS or SWS hyposalivation, and into a combined SWS and UWS hyposalivation category. Correlation and multivariable regression analyses were conducted to examine associations among SWS, MSF, UWS, XI, and anticholinergic burden, with adjustments made for age, sex, and comorbidities. RESULTS:SWS was moderately and significantly correlated with MSF. Lower SWS was also significantly correlated with lower UWS and greater xerostomia severity. Women exhibited significantly lower SWS and MSF flow rates and reported higher XI scores compared with men. Subjects with combined SWS and UWS hyposalivation had the lowest MSF rates, whereas participants without hyposalivation had the highest (p = 0.0002). CONCLUSIONS:Our findings indicate that SWS flow is associated with xerostomia severity and with UWS flow in adults with xerostomia taking anticholinergic medications. However, SWS and UWS hyposalivation did not always co-occur according to established thresholds, suggesting that measuring both may improve the characterization of salivary dysfunction.

Introduction:Anticholinergic medications frequently cause hyposalivation (decreased saliva flow) through parasympathetic inhibition. This adverse effect is related to anticholinergic burden, reflecting the cumulative exposure to drugs with anticholinergic properties. Genetic variation in CYP genes, which encode drug-metabolizing enzymes, alters drug metabolism, potentially influencing systemic anticholinergic burden. This study investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes are associated with anticholinergic burden and hyposalivation. Methods:Adults taking at least one CYP substrate anticholinergic medication reporting xerostomia (oral dryness) were recruited. Anticholinergic burden was quantified using the Anticholinergic Drug Scale (ADS) and Serum Anticholinergic Activity (SAA). Salivary assessment included unstimulated whole saliva (UWS) and minor saliva flow (MSF). Participants were genotyped for functional variants of CYP2D6 and CYP2C19. Results:CYP2D6 rs28371725 polymorphism was associated with low MSF and increased SAA in severe hyposalivation (genotype relative risk: 12.75, 95% CI 1.45-112.12). Additionally, variants (rs28371706, rs5030655) were associated with high ADS scores. Individuals with reduced CYP2D6 activity presented with higher systemic exposure and a greater anticholinergic burden for a given dose, as reflected by higher ADS and SAA. CYP2C19 polymorphisms showed no strong associations with salivary outcomes or anticholinergic burden. Conclusion:Genetic variation in CYP2D6 contributes to interindividual differences in systemic anticholinergic burden and hyposalivation. Pharmacogenetic profiling of CYP450 genes may help identify patients at risk of xerostomia from anticholinergic therapy, supporting more personalized and optimized anticholinergic prescribing.

Background: This cross-sectional study investigated the associations between medication-induced xerostomia (perceived oral dryness) and intraoral painful aching in 141 middle-aged adults (45-64 years) with self-reported xerostomia resulting from anticholinergic medications. Methods: Xerostomia severity, anxiety, and intraoral painful aching were evaluated using questionnaires, including the semiquantitative Xerostomia Inventory survey. Reduction in saliva secretion (hyposalivation) was objectively assessed by the measurement of unstimulated whole saliva (UWS) flow. Results: Multivariate stepwise linear regression was used to identify factors associated with XI scores, adjusting for potential confounders including age, sex, diabetes, smoking status, and race. The final model identified UWS flow (p = 0.0023), intraoral painful aching (p = 0.0030), and diabetes (p = 0.0097) as significant predictors of xerostomia severity. Anxiety demonstrated a marginal association (p = 0.0643) and accounted for a smaller proportion of model variance. Relative importance analysis revealed that UWS flow contributed 33.16% to the overall model fit, followed by intraoral pain (31.30%), diabetes (23.60%), and anxiety (11.93%). Conclusions: The findings indicate that reduced salivary flow, intraoral discomfort, and the presence of diabetes are significant contributors to xerostomia severity in individuals taking anticholinergic medications. These results highlight the importance of individualized evaluation in xerostomia care and inform targeted clinical strategies for managing xerostomia symptoms in patients with intraoral painful aching, anxiety, or comorbid diabetes.

PURPOSE:This study explored the relationship between central sensitization symptoms, assessed using the Central Sensitization Inventory (CSI), and psychophysical factors in patients with chronic masticatory myofascial pain (MMP) transitioning from the acute to chronic stages. METHODS:In this study, 23 patients with MMP and 22 healthy volunteers were assessed using psychophysical tests, including measurements of pressure pain threshold (PPT) and temporal summation of pain (TSP). Additionally, CSI scores were recorded to evaluate central sensitization symptoms. RESULTS:Patients with chronic MMP showed significantly lower PPT in all masticatory muscles and extratrigeminal areas compared with controls. However, there was no significant correlation between CSI scores and psychophysical test results in patients with MMP. CONCLUSION:The significant enhancement of TSP in patients with subchronic MMP suggests a potential role in the onset of myofascial pain. The main finding suggests that sub-chronic symptom patients show higher CSI scores despite no sensory testing changes, indicating that central sensitization possibly precedes observable symptoms.

BACKGROUND:Implementing the Age-Friendly Health System (AFHS) framework into dental care provides a significant opportunity to link oral health to healthy aging. This project aimed to implement the AFHS 4Ms (what matters, medications, mentation, and mobility) in the provision of oral health care. This article describes the planning, integration, training development, and outcome measurements supporting a 4Ms approach at an academic dental clinic. METHODS:The Eastman Institute for Oral Health (EIOH) implemented screening instruments based on the 4Ms framework recommended for ambulatory care clinics by the Institute for Health Care Improvement (IHI). These ambulatory instruments were integrated into the workflows of a Specialty Care Clinic through the development of a plan-do-study-act cycle, utilization of available clinic resources, and creation of interdisciplinary collaborations. RESULTS:This project demonstrated the feasibility of implementing an AFHS checklist and tracking forms in dental practice by integrating available resources and prioritizing the 4Ms elements. This effort necessitated interdisciplinary collaborations between dental, medical, and social service professionals. It also created a new age-friendly focused education and training curriculum for dental residents and faculty. CONCLUSIONS:This pilot project is the first to establish dental standards for AFHS implementation, adapting the 4Ms assessment and metrics to oral health. This AFHS underscores key oral health processes, including assessment, planning, and personalized oral health care, adapted to the unique needs of the older adult population, especially those with cognitive impairment.

Stress is a process that activates neuronal, metabolic, and neuroendocrine mechanisms. The individual's response may be determined by variables such as genetic factors, environmental conditions, sex, and age, among others. These responses are critical for survival, and the involvement of the hypothalamic-pituitary-adrenal axis is necessary for adaptation, which through counter-regulatory mechanisms seeks to restore homeostasis. Dentists are aware that there are variations in people's response to treatment, and there are many patients in whom dental treatment generates an important source of stress, which in many cases leads to treatment avoidance behavior.

Mechanisms underlying neuropathic pain (NP) are complex with multiple genes, their interactions, environmental and epigenetic factors being implicated. Transcriptional changes in the trigeminal (TG) and dorsal root (DRG) ganglia have been implicated in the development and main-tenance of NP. Despite efforts to unravel molecular mechanisms of NP, many remain unknown. Also, most of the studies focused on the spinal system. Although the spinal and trigeminal systems share some of the molecular mechanisms, differences exist. We used RNA-sequencing technology to identify differentially expressed genes (DEGs) in the TG and DRG at baseline and 3 time points fol-lowing the infraorbital or sciatic nerve injuries, respectively. Pathway analysis and comparison analysis were performed to identify differentially expressed pathways. Additionally, upstream reg-ulator effects were investigated in the two systems. DEG (differentially expressed genes) analyses identified 3,225 genes to be differentially expressed between TG and DRG in naive animals, 1,828 genes 4 days post injury, 5,644 at day 8 and 9,777 DEGs at 21 days postinjury. A comparison of top enriched canonical pathways revealed that a number of signaling pathway was significantly in-hibited in the TG and activated in the DRG at 21 days postinjury. Finally, CORT upstream regulator was predicted to be inhibited in the TG while expression levels of the CSF1 upstream regulator were significantly elevated in the DRG at 21 days postinjury. This study provides a basis for further in-depth studies investigating transcriptional changes, pathways, and upstream regulation in TG and DRG in rats exposed to peripheral nerve injuries. Perspective: Although trigeminal and dorsal root ganglia are homologs of each other, they re-spond differently to nerve injury and therefore treatment. Activation/inhibition of number of bio-logical pathways appear to be ganglion/system specific suggesting that different approaches might be required to successfully treat neuropathies induced by injuries in spinal and trigeminal systems. (R) 2023 Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc