Effect of soft denture liners on complete denture treatments: A systematic review.

PURPOSE: This systematic review examined the effectiveness of soft denture relining (SDR) materials. STUDY SELECTION: A comprehensive search of MEDLINE, Cochrane Library, and ICHUSHI was conducted up to July 26, 2020. Target outcomes were patient satisfaction, oral health-related quality of life (OHRQOL), masticatory ability (MA), denture functional duration, residual ridge resorption (RRR), and microbial contamination. An organization specializing in literature searches performed the reference searches, and two reviewers independently selected the literature sources, extracted the data, and assessed the risk of bias. The reviewers resolved any disagreements concerning the assortment of literature sources through discussion. SDR included acrylic- and silicone-based materials, which were evaluated separately. RESULTS: Reviewers selected 7, 5, 11, 1, 4, and 6 studies to assess patient satisfaction, OHRQOL, MA, functional duration, RRR, and microbial contamination, respectively. The results confirmed that SDR improved patient satisfaction, OHRQOL, MA, and RRR. However, the functional duration of SDR material is shorter than that of hard denture relining (HDR) or acrylic resin material. Furthermore, SDR material is more susceptible to microbial contamination in the long term. The risk of bias for the included studies tended to be high because of specific issues (difficulty in blinding SDR versus HDR). CONCLUSIONS: For patients who wear complete dentures, SDR often provides beneficial outcomes such as pain reduction and recovery from MA. However, caution should be exercised regarding their use owing to insufficient functional duration and the possibility of microbial contamination during long-term use.

A nested case-control study of factors contributing to the development of medication-related osteonecrosis of the jaw in patients using bone resorption inhibitors in Mishima City.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is characterized by necrosis of the jawbone with intraoral bacterial infection and has a significant negative impact on oral health-related quality of life. Risk factors for the onset are unknown, and definitive therapeutic approaches have not yet been defined. A case-control study at a single institution in Mishima City was conducted. The purpose of this study was to examine in detail the factors that contribute to the development of MRONJ. METHODS: Medical records of MRONJ patients who visited Mishima Dental Center, Nihon University School of Dentistry, during the period 2015-2021 were extracted. Counter-matched sampling design was used to select participants matched for sex, age, and smoking for this nested case-control study. The incidence factors were statistically examined by logistic regression analysis. RESULTS: Twelve MRONJ patients were used as cases and 32 controls were matched. After adjustment for potential confounders, injectable bisphosphonates (aOR = 24.5; 95% CI = 1.05, 575.0; P < 0.05) were significantly associated with the development of MRONJ. CONCLUSION: High-dose bisphosphonates may be a risk factor for the development of MRONJ. Patients who use these products require careful prophylactic dental treatment against inflammatory diseases, and dentists and physicians should maintain close communication.

Allograft inflammatory factor-1 released from the cerebral microglia affect several organs in the body.

Allograft inflammatory factor-1 (AIF-1) is expressed in microglia. Unilateral common carotid artery occlusion (UCCAO) was conducted to elucidate mechanisms that regulate AIF-1 expression in C57BL/6 male mice. Immunohistochemical reactivity of microglia against anti-AIF-1 antibody was increased significantly in the brain of this model. The increased AIF-1 production was further confirmed by ELISA using brain homogenate. Real-time PCR demonstrated that the increased AIF-1 production was regulated at the transcriptional level. Serum AIF-1 levels were further examined by ELISA and marked increase was observed on Day 1 of UCCAO. To examine the influence of AIF-1, immunohistochemical staining was performed and revealed that the immunoreactivity against anti-Iba-1 antibody was significantly increased in various organs. Among them, the accumulation of Iba-1+ cells were observed prominently in the spleen. Intraperitoneal injection of minocycline, a potent microglia inhibitor, reduced the number of Iba-1+ cells suggesting microglia activation-dependent accumulation. Based on these results, AIF-1 expression was further examined in the murine microglia cell line MG6. AIF-1 mRNA expression and secretion were up-regulated when the cells were cultured under hypoxic condition. Importantly, stimulation of the cells with recombinant AIF-1 induced the expression of AIF-1 mRNA. These results may suggest that increased AIF-1 production by microglia in cerebral ischemia regulate the AIF-1 mRNA expression at least in part by an autocrine manner.

Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury.

BACKGROUND/AIM: The ectopic pain associated with inferior alveolar nerve (IAN) injury has been reported to involve macrophage expression in the trigeminal ganglion (TG). However, the effect of age-related changes on this abnormal pain conditions are still unknown. This study sought to clarify the involvement of age-related changes in macrophage expression and phenotypic conversion in the TG and how these changes enhance ectopic mechanical allodynia after IAN transection (IANX). MATERIALS AND METHODS: We used senescence-accelerated mouse (SAM)-prone 8 (SAMP8) and SAM-resistance 1 (SAMR1) mice, which are commonly used to study ageing-related changes. Mechanical stimulation was applied to the whisker pad skin under light anaesthesia; the mechanical head withdrawal threshold (MHWT) was measured for 21 d post-IANX. We subsequently counted the numbers of Iba1 (macrophage marker)-immunoreactive (IR) cells, Iba1/CD11c (M1-like inflammatory macrophage marker)-co-IR cells, and Iba1/CD206 (M2-like anti-inflammatory macrophage marker)-co-IR cells in the TG innervating the whisker pad skin. After continuous intra-TG administration of liposomal clodronate Clophosome®-A (LCCA) to IANX-treated SAMP8-mice, the MHWT values of the whisker pad skin were examined. RESULTS: Five days post-IANX, the MHWT had significantly decreased in SAMP8 mice compared to SAMR1-mice. Iba1-IR and Iba1/CD11c-co-IR cell counts were significantly increased in SAMP8 mice compared to SAMR1 mice 5 d post-IANX. LCCA administration significantly restored MHWT compared to control-LCCA administration. CONCLUSION: Ectopic mechanical allodynia of whisker pad skin after IANX is exacerbated by ageing, which involves increases in M1-like inflammatory macrophages in the TG.

Relation between number of teeth, malnutrition, and 3-year mortality in elderly individuals ≥85 years.

OBJECTIVE: The number of teeth has been shown to affect mortality. However, it is unclear why the number of teeth is associated with mortality. We focused on the number of teeth and malnutrition and examined whether these differences affect 3-year all-cause mortality among very elderly individuals. METHODS: This analysis was conducted using data from the Tokyo Oldest Old Survey on Total Health study. Altogether 513 participants ≥85 years were categorized based on remaining teeth (0, 1-7, 8-18, ≥19). All-cause mortality was determined by calculating the cumulative 3-year survival rate according to the remaining number of teeth and the presence/absence of malnutrition. Further, hazard ratios (HRs) were analyzed using Cox regression analyses. RESULTS: No difference was observed according to the number of teeth (p = 0.638), but the presence/absence of malnutrition was significantly associated with mortality (p < 0.001). Malnutrition was independently associated with higher HRs, even after adjusting for confounding factors associated with mortality. (HR: 2.315, 95% CI: 1.431-3.746). Additionally, adjusting for the number of teeth, HR remained significant (HR: 2.365, 95% CI: 1.449-3.853). CONCLUSION: In the very elderly, malnutrition-but not the number of teeth-was independently associated with 3-year all-cause mortality after adjusting for various health issues.

Human Gingival Fibroblast Attachment to Smooth Titanium Disks with Different Surface Roughnesses.

Peri-implantitis is a significant problem associated with dental implants. It has been hypothesized that creating a soft-tissue seal around the implant neck prevents peri-implantitis. This study aims to clarify the effects of the surface smoothness of titanium disks on soft tissues. Thus, titanium disks were prepared through electrolytic composite polishing (ECP), sisal buffing (SB), hairline polishing (HP), and laser cutting (LC). The surface roughness values of seven items was measured. For ECP, SB, HP, and LC samples, the Ra values were 0.075, 0.217, 0.671, and 1.024 µm and the Sa values were 0.005, 0.115, 0.500, and 0.676, respectively, indicating that the surface roughness was remarkably lower with ECP. Moreover, the Wsk values for ECP, SB, HP, and LC were 0.521, 1.018, -0.678, and -0.558, respectively. The smooth surfaces produced by ECP and SB were biased toward the concave surface, whereas those produced by HP and LC were biased toward the convex surface. The Rku values for ECP, SB, HP, and LC were 2.984, 11.774, 14.182, and 26.232, respectively. Only the ECP exhibited a moderate bias peak and produced an extremely smooth surface. The contact angles in the cases of ECP, SB, HP, and LC were 60.1°, 66.3°, 68.4°, and 79.3°, respectively, indicating the hydrophobicity of the titanium disks. Human oral fibroblasts were then incubated on each disk for 24 and 48 h to measure cell attachment, and no significant differences were observed. The differences in Ra and Sa did not affect cell attachment. Therefore, by applying ECP to the abutment or implant neck, the cell attachment required for soft-tissue formation while preventing bacterial adhesion can be achieved.

Medication-related osteonecrosis of the jaw after tooth extraction in patients receiving pharmaceutical treatment for osteoporosis: A retrospective cohort study.

Background/purpose: Bone resorption inhibitors, such as bisphosphonates (BPs) and anti-receptor activator of nuclear factor kappa B ligand antibodies (denosumab; Dmab), are used to treat osteoporosis and effectively reduce the risk of fracture. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported as a rare adverse effect. Invasive tooth extraction procedures are reportedly a factor in the development of MRONJ. In this study, we aimed to retrospectively observe and clinically examine the effect of medication status on MRONJ development after tooth extraction in patients receiving drug treatment for osteoporosis. Materials and methods: This study was conducted among patients who visited our hospital between December 2015 and December 2021. We collected and analyzed the medical information of patients who underwent dental extractions while using osteoporosis medications, including oral and injectable BPs and Dmab. Results: Among antiresorptive medication users, 40 patients (70 teeth) underwent extraction. The mean duration of BP/Dmab use was 40.4 months, and the mean duration of drug holiday was 6.9 months. MRONJ after tooth extraction was not seen in BP users, but we observed two cases in Dmab users. A significant difference in MRONJ development was confirmed with the use of injectable compared with oral medication administration (odds ratio＝5.01). Conclusion: The use of injectable bone resorption inhibitors was associated with a higher risk of developing MRONJ. The route of administration, duration of medication, and withdrawal period should be carefully considered to prevent MRONJ after tooth extraction.

Effectiveness of Acid-electrolyzed Functional Water for Mouth Wash: An In Vitro Study.

BACKGROUND/AIM: Acid-electrolyzed functional water (FW) is an efficient bactericide and gargling with FW might be an effective method of oral care. We investigated the possible use of FW as a mouth wash by an in vitro study. MATERIALS AND METHODS: The bactericidal effect of FW against different species of bacteria (Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa, and Candida albicans) was evaluated using the numbers of colony-forming units (CFU). The experiment was conducted using PBS, LISTERINE, and ConCool F (undiluted, and the optimal concentration indicated). To investigate the bactericidal mechanism of FW, the activity of superoxide dismutase (SOD), an indicator of oxidative action, was measured in S. aureus. FW was diluted with purified water to concentrations of 10, 30, 50, and 70%. The numbers of CFU were measured for each concentration. XTT assays were performed using HSC-3 and HeLa cells, to examine the viability of the cells following treatment with FW. The same experiment was conducted with PBS, LISTERINE, and undiluted ConCool F. RESULTS: No bacteria treated with FW formed colonies. SOD activity peaked at a 50% concentration of FW and was more than twice that of the control. A significant decrease in the number of CFU was observed following 50% treatment. Since the peaks of the SOD activity and the starting concentrations of the bactericidal effects coincided, the bactericidal effect of FW might be related to its oxidative effects. Bacteria treated with FW had the same survival rate as the other mouth washes. CONCLUSION: FW might be clinically applicable as a mouth wash.

Age-Related Differences in Transient Receptor Potential Vanilloid 1 and 2 Expression Patterns in the Trigeminal Ganglion Neurons Contribute to Changes in the Palatal Mucosal Heat Pain Sensitivity.

Aging affects various sensory functions of the body. However, the effect on the oral mucosal nociception has remain unclear, so this elucidation is very important. Therefore, this study aimed to evaluate the effect of age-related changes in transient receptor potential vanilloid 1 (TRPV1) and TRPV2 expression in the trigeminal ganglion (TG) neurons on intraoral mucosal heat sensitivity in the senescence-accelerated mouse prone 8 (SAMP8) model. We used 23-week-old (aged) and 7-week-old (young) SAMP8 mice. Heat stimulation was applied to the palatal mucosa under light anesthesia; moreover, the heat head withdrawal threshold (HHWT) was measured. We counted the number of TRPV1-immunoreactive (IR) and TRPV2-IR TG neurons innervating the palatal mucosa. Additionally, we investigated changes in HHWT when TRPV1 or TRPV2 antagonists (SB366791 or Tranilast) were administered to the palatal mucosa. Aged SAMP8 mice showed a higher HHWT than young SAMP8 mice. Compared with the aged SAMP8 mice, young SAMP8 mice showed a larger number of TRPV1-IR small-diameter neurons and a smaller number of TRPV2-IR medium-sized neurons innervating the palatal mucosa. SB366791 administration increased the HHWT in young, but not aged SAMP8 mice. Contrastingly, Tranilast administration increased the HHWT in aged, but not young SAMP8 mice. These results suggest that the modulation of heat pain sensitivity in the oral mucosa due to aging is dependent on changes in the TRPV1 and TRPV2 expression patterns in the TG neurons innervating the palatal mucosa.

Porphyromonas gingivalis Mfa1 fimbria putatively binds to TLR2 and induces both IL-6 and IL-8 production in human bronchial epithelial cells.

Porphyromonas gingivalis (Pg) a major periodontal pathogen involved in periodontal disease development and progression. Moreover, Pg has two fimbriae surface proteins (FimA and Mfa1) that are genetically distinct and make-up the fimbrial shaft which in-turn form crucial attachment to oral bacteria and multiple host cells. However, unlike FimA, Mfa1 attachment to non-periodontal cells has not been fully elucidated. Considering Pg-associated periodontal disease contributes to pulmonary disease development, we investigated whether Mfa1 can functionally interact with human bronchial epithelial cells and, likewise, trigger a functional response. Initially, we simulated molecular docking and performed both luciferase and neutralization assays to confirm Mfa1-related functional interaction. Subsequently, we treated BEAS-2B cells with purified Mfa1 and performed cytokine quantification through real time-PCR and ELISA to establish Mfa1-related functional response. We found that both Mfa1-TLR2 and Mfa1-TLR4 docking is possible, however, only Mfa1-TLR2 showed a functional interaction. Additionally, we observed that both IL-8 and IL-6 gene expression and protein levels were induced confirming Mfa1-related functional response. Taken together, we propose that BEAS-2B human bronchial epithelial cells are able to recognize Pg Mfa1 and induce both IL-8 and IL-6 inflammatory responses.

Relationship between the oral cavity and respiratory diseases: Aspiration of oral bacteria possibly contributes to the progression of lower airway inflammation.

The global population is aging, and elderly people have a higher incidence of lower airway diseases owing to decline in swallowing function, airway ciliary motility, and overall immunity associated with aging. Furthermore, lower airway diseases in the elderly tend to have a high mortality rate. Their prevention is important for extending healthy life expectancy and improving the quality of life of each individual. In recent years, the relationship between "chronic periodontitis and oral bacteria, especially the periodontopathic ones" and "respiratory diseases" (e.g., pneumonia, chronic obstructive pulmonary disease, and influenza) has become clear. In addition, the association of several periodontal pathogens with the onset and aggravation of coronavirus disease 2019 (COVID-19) is also being reported. In support of these findings, oral health management has shown to reduce deaths from pneumonia and prevent influenza in nursing homes and inpatient wards. This has led to clinical and multidisciplinary cooperation between physicians and dentists, among others. However, to date, the mechanisms by which "chronic periodontitis and oral bacteria" contribute to lower airway diseases have not been well understood. Clarifying these mechanisms will lead to a theoretical basis for answering the question, "Why is oral health management effective in preventing lower airway diseases?"

Associations of poor oral health with frailty and physical functioning in the oldest old: results from two studies in England and Japan.

BACKGROUND: Very few studies have examined the relationship of oral health with physical functioning and frailty in the oldest old (> 85 years). We examined the association of poor oral health with markers of disability, physical function and frailty in studies of oldest old in England and Japan. METHODS: The Newcastle 85+ Study in England (n = 853) and the Tokyo Oldest Old Survey on Total Health (TOOTH; n = 542) comprise random samples of people aged > 85 years. Oral health markers included tooth loss, dryness of mouth, difficulty swallowing and difficulty eating due to dental problems. Physical functioning was based on grip strength and gait speed; disability was assessed as mobility limitations. Frailty was ascertained using the Fried frailty phenotype. Cross-sectional analyses were undertaken using logistic regression. RESULTS: In the Newcastle 85+ Study, dry mouth symptoms, difficulty swallowing, difficulty eating, and tooth loss were associated with increased risks of mobility limitations after adjustment for sex, socioeconomic position, behavioural factors and co-morbidities [odds ratios (95%CIs) were 1.76 (1.26-2.46); 2.52 (1.56-4.08); 2.89 (1.52-5.50); 2.59 (1.44-4.65) respectively]. Similar results were observed for slow gait speed. Difficulty eating was associated with weak grip strength and frailty on full adjustment. In the TOOTH Study, difficulty eating was associated with increased risks of frailty, mobility limitations and slow gait speed; and complete tooth loss was associated with increased risk of frailty. CONCLUSION: Different markers of poor oral health are independently associated with worse physical functioning and frailty in the oldest old age groups. Research to understand the underlying pathways is needed.

Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.

Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19.

Coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic in March 2020 by the World Health Organization. Periodontitis, one of the most prevalent diseases worldwide, leads to alveolar bone destruction and subsequent tooth loss, and develops due to pro-inflammatory cytokine production induced by periodontopathic bacteria. Periodontopathic bacteria are involved in respiratory diseases, including aspiration pneumonia and chronic obstructive pulmonary disease (COPD), and other systemic diseases, such as diabetes and cardiovascular disease. Patients with these diseases have an increased COVID-19 aggravation rate and mortality. Because aspiration of periodontopathic bacteria induces the expression of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, and production of inflammatory cytokines in the lower respiratory tract, poor oral hygiene can lead to COVID-19 aggravation. Conversely, oral care, including periodontal treatment, prevents the onset of pneumonia and influenza and the exacerbation of COPD. The reduced chance of receiving professional oral care owing to long-term hospitalization of patients with COVID-19 may increase the aggravation risk of infection in the lower respiratory tract. It can be hypothesized that periodontopathic bacteria are involved in the COVID-19 aggravation and therefore, the management of good oral hygiene potentially contributes to its prevention.

Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity.

Activated microglia involved in the development of orofacial pain hypersensitivity have two major polarization states. The aim of this study was to assess the involvement of the aging-related phenotypic conversion of medullary microglia in the enhancement of intraoral pain sensitivity using senescence-accelerated mice (SAM)-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) mice. Mechanical head-withdrawal threshold (MHWT) was measured for 21 days post palatal mucosal incision. The number of CD11c-immunoreactive (IR) cells [affective microglia (M1)] and CD163-IR cells [protective microglia (M2)], and tumor-necrosis-factor-α (TNF-α)-IR M1 and interleukin (IL)-10-IR M2 were analyzed via immunohistochemistry on days 3 and 11 following incision. The decrease in MHWT observed following incision was enhanced in SAMP8 mice. M1 levels and the number of TNF-α-IR M1 were increased on day 3 in SAMP8 mice compared with those in SAMR1 mice. On day 11, M1 and M2 activation was observed in both groups, whereas IL-10-IR M2 levels were attenuated in SAMP8 mice, and the number of TNF-α-IR M1 cells increased, compared to those in SAMR1 mice. These results suggest that the mechanical allodynia observed following intraoral injury is potentiated and sustained in SAMP8 mice due to enhancement of TNF-α signaling, M1 activation, and an attenuation of M2 activation accompanying IL-10 release.

Involvement of Satellite Cell Activation via Nitric Oxide Signaling in Ectopic Orofacial Hypersensitivity.

: The mechanical head-withdrawal threshold (MHWT) was significantly reduced following inferior alveolar nerve transection (IANX) in rats. Nitrate and nitrite synthesis was dramatically increased in the trigeminal ganglion (TG) at 6 h after the IANX. The relative number of neuronal nitric oxide synthase (nNOS)-immunoreactive (IR) cells was significantly higher in IANX rats compared to sham-operated and N-propyl-L-arginine (NPLA)-treated IANX rats. On day 3 after NPLA administration, the MHWT recovered considerably in IANX rats. Following L-arginine injection into the TG, the MHWT was significantly reduced within 15 min, and the mean number of TG cells encircled by glial fibrillary acidic protein (GFAP)-IR cells was substantially higher. The relative number of nNOS-IR cells encircled by GFAP-IR cells was significantly increased in IANX rats. In contrast, after NPLA injection into the TG, the relative number of GFAP-IR cells was considerably reduced in IANX rats. Fluorocitrate administration into the TG significantly reduced the number of GFAP-IR cells and prevented the MHWT reduction in IANX rats. The present findings suggest that following IANX, satellite glial cells are activated via nitric oxide (NO) signaling from TG neurons. The spreading satellite glial cell activation within the TG results in mechanical hypersensitivity of face regions not directly associated with the trigeminal nerve injury.

Functional involvement of nucleus tractus solitarii neurons projecting to the parabrachial nucleus in trigeminal neuropathic pain.

Peripheral nerve injury can induce neuroplastic changes in the central nervous system and result in neuropathic pain. This study investigated functional involvement in dorsal paratrigeminal nucleus (dPa5) and nucleus tractus solitarii (NTS) neurons projecting to the parabrachial nucleus (PBN) after trigeminal nerve injury. Anatomical quantification was performed based on phosphorylated extracellular signal-regulated kinase (pERK) expression underlying orofacial neuropathic pain associated with infraorbital nerve chronic constriction injury (ION-CCI) in rats. ION-CCI rats exhibited heat and mechanical hypersensitivity in the ipsilateral upper lip. After injection of retrograde tracer fluorogold (FG) into the contralateral PBN, ION-CCI rats received capsaicin or noxious mechanical stimulation to the upper lip. The total number of FG-labeled neurons in dPa5 and NTS did not change after ION-CCI, and pERK expression in dPa5 did not differ between sham and ION-CCI rats. In the NTS contralateral to ION-CCI, the number of pERK-immunoreactive neurons and percentage of pERK-immunoreactive FG-labeled PBN projection neurons were increased after capsaicin stimulation in ION-CCI rats. The present findings suggest that enhanced noxious inputs from the NTS to the PBN after trigeminal nerve injury modulates PBN neuron activity, which accompanies the affective components of orofacial neuropathic pain.

Upregulation of calcitonin gene-related peptide, neuronal nitric oxide synthase, and phosphorylated extracellular signal-regulated kinase 1/2 in the trigeminal ganglion after bright light stimulation of the eye in rats.

Bright light stimulation of the eye activates trigeminal subnucleus caudalis (Vc) neurons in rats. Sensory information is conveyed to the Vc via the trigeminal ganglion (TG). Thus, it is likely that TG neurons respond to photic stimulation and are involved in photic hypersensitivity. However, the mechanisms underlying this process are unclear. Therefore, the hypothesis in this study is bright light stimulation enhances the excitability of TG neurons involved in photic hypersensitivity. Expressions of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase (nNOS) were significantly higher in TG neurons from 5 min to 12 h after photic stimulation of the eye. Phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) was enhanced in TG neurons within 5 min after photic stimulation, while pERK1/2 immunoreactivity in satellite glial cells (SGCs) persisted for more than 12 h after the stimulus. Activation of SGCs was observed from 5 min to 2 h. Expression of CGRP, nNOS, and pERK1/2 was observed in small and medium TG neurons, and activation of SGCs and pERK1/2-immunoreactive SGCs encircling large TG neurons was accelerated after stimulation. These results suggest that upregulation of CGRP, nNOS, and pERK1/2 within the TG is involved in photic hypersensitivity.

Differential activation of ascending noxious pathways associated with trigeminal nerve injury.

Trigeminal spinal subnucleus caudalis (Vc) neurons that project to the ventral posteromedial thalamic nucleus (VPM) and parabrachial nucleus (PBN) are critical for orofacial pain processing. We hypothesized that persistent trigeminal nerve injury differentially alters the proportion of Vc neurons that project to VPM and PBN in a modality-specific manner. Neuroanatomical approaches were used to quantify the number of Vc neurons projecting to VPM or PBN after chronic constriction injury of the infraorbital nerve (ION-CCI) and subsequent upper-lip stimulation. Male rats received injections of retrograde tracer fluorogold into the contralateral VPM or PBN on day 7 after ION-CCI, and at 3 days after that, either capsaicin injection or noxious mechanical stimulation was applied to the upper lip ipsilateral to nerve injury. Infraorbital nerve chronic constriction injury rats displayed greater forelimb wiping to capsaicin injection and mechanical allodynia of the lip than sham rats. Total cell counts for phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons after capsaicin or mechanical lip stimuli were higher in ION-CCI than sham rats as was the percentage of pERK-IR PBN projection neurons. However, the percentage of pERK-IR VPM projection neurons was also greater in ION-CCI than sham rats after capsaicin but not mechanical lip stimuli. The present findings suggest that persistent trigeminal nerve injury increases the number of Vc neurons activated by capsaicin or mechanical lip stimuli. By contrast, trigeminal nerve injury modifies the proportion of Vc nociceptive neurons projecting to VPM and PBN in a stimulus modality-specific manner and may reflect differential involvement of ascending pain pathways receiving C fiber and mechanosensitive afferents.

Prefrontal cortex activity during swallowing in dysphagia patients.

Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z-scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food.