Relief Of Hypersensitivity Research Articles

Silver Diamine Fluoride Renaissance in Paediatric Dentistry: A 24-Month Retrospective and Cross-Sectional Analysis.

Background and Objectives: Silver diamine fluoride (SDF) has been incorporated into the treatment of dental caries in children, mainly in countries with high caries prevalence. In Europe, however, SDF started to gain popularity during the COVID-19 pandemic. This study aimed to investigate the efficacy of SDF and to evaluate dentists'/parents' acceptance of SDF use in paediatric patients treated in a German university setting. Materials and Methods: A retrospective analysis of all patients treated with SDF between 2017 and 2020 was carried out. Only teeth with no reported clinical/radiographic evidence of irreversible pulpal inflammation were included. The outcome measures were success, minor failures (caries progression, reversible pulpitis) and major failures (irreversible pulpitis, abscess). The treatment acceptance by dentists and the parents of SDF-treated children was cross-sectionally evaluated using questionnaires. Descriptive statistics and Kaplan-Meier survival analysis were performed. Results: A total of 93 patients (mean age 5.3 ± 2.9 years) with 455 treated teeth (418 primary/91.9%; 37 permanent/8.1%) were included and followed up for up to 24 months (19.9 ± 10.5 months). SDF was used for dental caries (98.2%) and hypersensitivity relief on MIH teeth (1.8%). Most teeth did not show any failure (total success 84.2%). A total of 5 teeth (1.1%) showed minor failures, and 67 teeth (14.7%) showed major failures (p = 0.001). Success/failure rates were not affected by patient compliance, gender, dentition, or operator (p > 0.05). In total, 30 questionnaires were collected from parents (mean age 36.8 ± 6.4 years). SDF was applied on anterior (n = 2/6.7%), posterior (n = 15/50%) and anterior/posterior teeth (n = 13/43.3%). At the 1-week follow-up, 80% of parents noticed black teeth discoloration. Treatment satisfaction was higher for posterior (95.2%) than for anterior teeth (36.4%; p < 0.001). In the 27 responses from clinicians, SDF was generally considered a viable option in paediatric dentistry (n = 23; 85%). Conclusions: SDF was found to be effective and well-accepted by parents and dentists for caries inactivation in a paediatric dentistry German university setting.

Efficacy of Different Fluoride Therapies on Hypersensitive Carious Lesions in Primary Teeth.

Background and Objectives: This prospective, comparative, double-cohort study aimed to compare the efficacy of silver diamine fluoride and potassium iodide (38% SDF+KI; Riva Star®) with sodium fluoride varnish (5% NaF; Duraphat®) in hypersensitive carious lesions in primary teeth to evaluate caries arrest and hypersensitivity relief. Materials and Methods: This study included thirty 2-5-year-olds (mean age = 3.67 ± 1.06 years; 16 males and 14 females) who required a desensitizing treatment for hypersensitive carious defects with visible dentin. A total of 15 of the participants were consecutively allocated to treatment with 5% NaF, and they were further compared to an equal number of participants treated with 38% SDF+KI solutions (n = 15). The treatments were performed following clinical evaluation of caries activity using the International Caries Classification and Management System (ICCMSTM) and the Bjørndal criteria (score of 0-9). Parental-reported hypersensitivity was evaluated using a visual analogue scale (0-10 = no to severe pain). Results: Clinical variables were evaluated at baseline and three months after treatment. Thereafter, a significant decline in hypersensitivity/pain led to lower final scores in the Riva Star® group (0.40 ± 1.12, p = 0.002) than in the Duraphat® group (1.40 ± 2.20, p = 0.004). The caries arrest effect was significantly higher in the Riva Star® group (86.7%) compared to the Duraphat® group three months after treatment (13.3%, p < 0.001). In both groups, there were no statistically significant differences in the children's behavior before, during, and after treatment. Conclusions: Ultimately, with both fluoride therapies reducing hypersensitivity/pain significantly, treatment with 38% SDF+KI was clearly more effective in caries arrest than 5% NaF varnish after a 3-month period.

Ankle Audiometry: A Clinical Test for the Enhanced Hearing Sensitivity for Body Sounds in Superior Canal Dehiscence Syndrome

Introduction: The aim of this study was to develop a clinical test for body sounds’ hypersensitivity in superior canal dehiscence syndrome (SCDS). Method: Case-control study, 20 patients affected by SCDS and body sounds’ hypersensitivity and 20 control matched subjects tested with a new test called ankle audiometry (AA). The AA consisted of a psychoacoustic hearing test in which the stimulus was substituted by a controlled bone vibration at 125, 250, 500, and 750 Hz, delivered at the medial malleolus by a steel spring-attached bone transducer prototype B250. For each subject, it was defined an index side (the other being non-index), the one with major symptoms in cases or best threshold for each tested frequency in controls. In 3 patients, the AA was measured before and after SCDS surgery. Results: The AA thresholds for index side were significantly lower in SCDS patients (115.6 ± 10.5 dB force level [FL]) than in control subjects (126.4 ± 8.56 dB FL). In particular, the largest difference was observed at 250 Hz (−16.5 dB). AA thresholds in patients were significantly lower at index side in comparison with non-index side (124.2 ± 11.4 dB FL). The response obtained with 250 Hz stimuli outperformed the other frequencies, in terms of diagnostic accuracy for SCDS. At specific thresholds’ levels (120 dB FL), AA showed relevant sensitivity (90%) and specificity (80%) for SCDS. AA did not significantly correlate to other clinical markers of SCDS such as the bone and air conducted hearing thresholds and the vestibular evoked myogenic potentials. The AA thresholds were significantly modified by surgical intervention, passing from 119.2 ± 9.7 to 130.4 ± 9.4 dB FL in 3 patients, following their relief in body sounds’ hypersensitivity. Conclusion: AA showed interesting diagnostic features in SCDS with significantly lower hearing thresholds in SCDS patients when compared to healthy matched subjects. Moreover, AA could identify the affected or more affected side in SCDS patients, with a significant threshold elevation after SCDS surgery, corresponding in body sounds’ hypersensitivity relief. Clinically, AA may represent a first objective measure of body sounds’ hypersensitivity in SCDS and, accordingly, be an accessible screening test for SCDS in not tertiary audiological centers.

Targeting TRPV1 activity via high-dose capsaicin in patients with sickle cell disease.

Evidence suggests neuropathic pain (NP) develops over time in sickle cell disease (SCD), contributing to a complex, difficult‐to‐treat phenotype, with management based on scant evidence. One characteristic of NP found is hyperalgesia caused by nervous system sensitization, but risk factors for this have not been identified within the SCD population, as exact mechanisms leading to its development are not well defined. The SPICE (Sickle cell Pain: Intervention with Capsaicin Exposure) trial was a pilot safety and feasibility trial of high‐dose (8%) topical capsaicin for patients with SCD and recurrent/chronic pain with neuropathic features, aimed at exploring capsaicin's utility as a mechanistic probe and adjunctive pain treatment for this population. Ten participants identifying “target” sites of pain with NP‐type qualities consented to treatment. The primary endpoint was safety/tolerability. The novel Localized Peripheral Hypersensitivity Relief score (LPHR) was developed to determine improvement in sensitivity attributable to TRPV1 neutralization. There were no severe treatment‐related adverse events. Higher baseline pain sensitivity at a given body site was associated with self‐reported history of more frequent localized vaso‐occlusive pain episodes at that site. There was a statistically significant improvement in the mean LPHR, evidencing TRPV1's importance to the development of hypersensitivity and a potential therapeutic benefit of capsaicin for SCD.

Hydroxyapatite as Remineralization Agent for Children's Dental Care

Children are prone to develop dental caries. This is supported by epidemiological data confirming early childhood caries (ECC) as a highly prevalent disease affecting more than every second child worldwide. ECC is known to result from an imbalance between re- and demineralization where demineralization dominates due to frequent acid production by cariogenic bacteria present in oral biofilms. The application of oral care formulations containing remineralizing agents helps to prevent dental caries. As young children are sensitive and usually swallow (intended or unintended) a majority of toothpaste or other oral care products during daily dental care, all ingredients, especially the actives, should be non-toxic. Biomimetic hydroxyapatite [HAP; Ca5(PO4)3(OH)] is known to have favorable remineralizing properties combined with an excellent biocompatibility, i.e., it is safe if accidently swallowed. Several clinical trials as well as in situ and in vitro studies have shown that HAP remineralizes enamel and dentin. Remineralization occurs due to deposition of HAP particles on tooth surfaces forming mineral-mineral bridges with enamel crystals, but also indirectly through calcium and phosphate ions release as well as HAP's buffering properties in acidic environments (i.e., in plaque). HAP induces a homogenous remineralization throughout the subsurface enamel lesions. This review summarizes the current evidence showing HAP as an effective remineralizing agent in oral care products for children. Additional studies showing also further beneficial effects of HAP such as the reduction of biofilm formation and the relief of hypersensitivity in children with molar incisor hypomineralization (MIH). It can be concluded that HAP is an effective and safe remineralizing agent for child dental care.

Neuronal allodynic mechanisms of Slc7a5 (LAT1) in the spared nerve injury rodent model of neuropathic pain.

High-impact chronic pain is suffered by 1 in 5 patients in the USA and globally. Effective, non-addictive, non-opioid therapeutics are urgently needed for the treatment of chronic pain. Slc7a5 (Lat1), also known as system L-neutral amino acid transporter, is involved in a number of physiological processes related to inflammation. Transcriptomics studies have shown that Slc7a5 and its binding partner Slc3a2 are expressed in neurons of the dorsal root ganglia (DRG) and spinal dorsal horn, which are critical to the initiation and maintenance of nociception and pathophysiology of chronic pain. In addition, Slc7a5 is a transporter for the first-line anti-allodynic gabapentinoid drugs and binds to ion channels implicated in nociception and chronic pain including the voltage-gated sodium channel Nav1.7 and the voltage-gated potassium channels Kv1.1 and Kv1.2. We found that blocking Slc7a5 with intrathecal administration of the drug JPH203 alleviated allodynia in the spared nerve injury (SNI) rodent model of neuropathic pain. Western blot and immunohistochemistry studies revealed an increase in Slc7a5 protein levels in the spinal cord and DRGs of SNI mice compared to control mice. Using whole-cell current-clamp electrophysiology, we observed that JPH203 treatment reduced excitability of small-diameter (< 30µm) DRG neurons from SNI mice, in agreement with its behavioral effects. Voltage-clamp recordings from JPH203-treated naïve rat DRGs identified an effect on tetrodotoxin-resistant (TTX-R) sodium currents. Altogether, these results demonstrate that Slc7a5 is dysregulated in chronic neuropathic pain and can be targeted to provide relief of hypersensitivity.

Efficacy of a Toothpaste Based on Microcrystalline Hydroxyapatite on Children with Hypersensitivity Caused by MIH: A Randomised Controlled Trial.

Hypersensitivity is a frequent complaint in children with molar incisor hypomineralisation (MIH). This double-blind randomised controlled trial aimed to evaluate non-inferiority in hypersensitivity relief of a toothpaste containing microcrystalline hydroxyapatite compared to amine fluoride in children with MIH. Children were randomised into 2 groups: either hydroxyapatite (intervention) or amine fluoride toothpaste (control). The primary endpoint was pain sensation in response to tactile stimulus (Wong-Baker FACES Pain Rating Scale) 56 days after randomisation and analysed by mixed effects linear regression analysis. Non-inferiority was inferred if the upper limit of the one-sided 95% confidence interval (CI) of the difference between intervention and control group was below the non-inferiority margin of 1 in the ITT (intention-to-treat) and PP (per protocol) population. Twenty-one children were randomised and 14 children finished the study per protocol. In the ITT population, hydroxyapatite was non-inferior to amine fluoride (mean difference: -0.75 95%CI [-∞;0.49]). In the PP population, non-inferiority could not be shown (-0.62 [-∞;1.08]). Overall non-inferiority in hypersensitivity relief of a toothpaste containing hydroxyapatite compared to amine fluoride could not be shown. However, the hydroxyapatite group tended to be less hypersensitive in both populations. Attrition of the PP population due to the COVID-19 pandemic led to loss of statistical power.

Hypersensitivity relief of MIH-affected molars using two sealing techniques: a 12-week follow-up

ObjectivesThe aim of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 12 weeks after sealing using two different materials (composite and glass ionomer). Furthermore, the retention rates of both materials were analyzed.MethodsThirty-nine children with two MIH-affected molars showing hypersensitivity and non-occlusal breakdowns were included. Hypersensitivity was assessed with an evaporative (air) stimulus. Both teeth were sealed by two calibrated operators using a split-mouth design with either Clinpro Sealant in combination with Scotchbond Universal (C) or Ketac Universal (K), respectively. Clinical pain assessments (Schiff Score Air Sensitivity Scale [SCASS], Visual Analog Scale [VAS]) were made at baseline (“pre”), immediately after treatment (“post”), and after 1, 4, 8, and 12 weeks. Paired t tests were calculated in each group between baseline and all other time points.ResultsThirty-eight children with 76 molars completed all stages of the study. Regardless of the material used, the application of the sealant decreased hypersensitivity significantly immediately as well as throughout the 12-week recalls (all p values < 0.001). We found no statistically significant difference among both materials chosen in any of the time points evaluated. Furthermore, retention of both materials was comparable in both groups.ConclusionsBoth sealant materials were able to reduce hypersensitivity successfully immediately and throughout the 12-week follow-up. Furthermore, their performance was similar in terms of retention.Clinical relevanceHypersensitivity can be a major complaint in patients with MIH. This is the first study evaluating hypersensitivity relief of MIH-affected molars using two sealing techniques.

Efficacy of an anhydrous stannous fluoride toothpaste for relief of dentine hypersensitivity: A randomized clinical study.

AimTo compare efficacy of an anhydrous 0.454% w/w stannous fluoride/sodium fluoride toothpaste (Test) versus a sodium monofluorophosphate toothpaste (Negative control) and a stannous chloride/sodium fluoride toothpaste (Positive control) for dentine hypersensitivity relief after 8 weeks’ twice‐daily use.Materials and MethodsIn this randomized, examiner‐blind, stratified, parallel study, primary and secondary efficacy variables were mean changes in Schiff score (evaporative [air] sensitivity) and tactile threshold (Yeaple probe), respectively, from baseline to Week 8 between Test (n = 62) and Negative control (n = 62). Test and Positive control (n = 61) comparisons were exploratory objectives.ResultsAll groups significantly improved from baseline on both dentine hypersensitivity measures (p < .0001). Difference between adjusted mean changes from baseline in Schiff sensitivity scores at Week 8 for Test versus Negative control groups was 0.19 (95% CI 0.002, 0.374), in favour of the Negative control (p = .0476; 12.57% difference). Difference in tactile threshold was −7.20 g (95% CI −16.376, 1.975), and this was not statistically significant (p = .3715; −21.83% difference). Test group showed no significant difference versus Positive control for either measure. Toothpastes were generally well tolerated.ConclusionWhile twice‐daily use of Test toothpaste significantly reduced dentine hypersensitivity from baseline, there was no significant advantage over negative or positive controls. Study registration: Clinicaltrials.gov; NCT03310268.

Randomised clinical studies investigating immediate and short-term efficacy of an occluding toothpaste in providing dentine hypersensitivity relief

BackgroundDentine hypersensitivity (DH) can occur after gum recession or enamel loss and may impact quality of life. Treatments include toothpastes that decrease DH by occluding dentine tubules. One effective occluding ingredient used in toothpastes is stannous fluoride (SnF2), but this can be unstable in aqueous formulation. These three studies aimed to characterise the short-term effects of an experimental, anhydrous SnF2 dentifrice on DH.MethodsThree examiner-blind, parallel-group studies evaluated DH in participants with the condition after a single brushing and after 3d brushing with an experimental anhydrous 0.454% SnF2/polyphosphate toothpaste (Test) or a toothpaste containing 0.76% sodium monofluorophosphate (Control). Test treatment participants brushed two pre-identified sensitive teeth first, then their remaining dentition for ≥1 min (‘focused brushing’). Control treatment participants brushed their whole dentition for ≥1 min. DH was measured after single brushing and after 3d twice-daily use, via evaporative (air) (Schiff Sensitivity Scale) and tactile (Yeaple probe) stimuli and analysed using an ANCOVA model.ResultsIn all studies, after 3d treatment, the Test toothpaste/brushing regimen significantly reduced DH compared to the Control regimen by both evaporative and tactile stimuli assessment (p < 0.0001 for all). The Test regimen also significantly reduced DH from baseline at both time-points by both measures in all studies (p < 0.0001 for all).Mean Schiff sensitivity score differences (95% confidence intervals) between Test and Control regimens after 3d were: Study 1: − 0.45 (− 0.577, − 0.319); Study 2: − 0.40 (− 0.505, − 0.300); Study 3: − 1.31 (− 1.500, − 1.128). Mean tactile score differences were: Study 1: 11.30 (7.927, 14.662); Study 2: 3.57 (2.531, 4.614); Study 3: 24.54 (20.349, 28.736). After single use, in Studies 2 and 3, the Test toothpaste/brushing regimen significantly reduced DH versus Control by both measures (p < 0.001 for all); in Study 1, treatment differences were not significant. Toothpastes were generally well-tolerated.ConclusionsTaken together, these studies indicated focused brushing with an experimental anhydrous 0.454% SnF2/polyphosphate toothpaste reduces DH compared to brushing with a conventional toothpaste after single use, with greater reduction after 3d.Trial registrationRegistrations at ClinicalTrials.gov: Study 1: NCT02832375 (registered 26.July.2016); Study 2: NCT02731833 (registered 26.April.2016); Study 3: NCT02923895 (registered 5.October.2016).

Efficacy of a dissolvable strip with calcium sodium phosphosilicate (NovaMin®) in providing rapid dentine hypersensitivity relief

ObjectiveTo evaluate the efficacy of a dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) (Novamin®) in providing rapid relief from dentine hypersensitivity (DH). MethodsIn this examiner-blind, proof-of-principle study, 120 healthy adults with DH were randomized 1:1 to the Test strip, professionally applied to facial surfaces of two selected teeth, or to No treatment. Sensitivity was assessed at baseline and 10min, 2h and 4h post-application in response to evaporative (air) and tactile stimuli (measured by Schiff sensitivity scale/a numeric rating scale and tactile threshold, respectively). Change from baseline was analyzed by ANCOVA. ResultsAt 10min post-application, mean Schiff score change from baseline (primary endpoint) was statistically significant with the Test strip (−0.46; 95% confidence intervals [CI]: −0.563, −0.356; p<0.0001) but not with No treatment (−0.02; 95% CI: −0.119, 0.088; p=0.7664). The between-treatment group difference favored the Test strip (difference: −0.44; 95% CI: −0.591, −0.297; p<0.0001). Similar improvements with the Test strip were reported for all other evaporative (air) and tactile sensitivity endpoints (p<0.0001 vs no-treatment) at all timepoints (10min, 2h, 4h). Test strips were considered by most staff and participants slightly/moderately easy to apply (98%). Many participants rated the overall usage experience as “like moderately” (40%) or “like extremely” (20%). There were no treatment-related adverse events. ConclusionThis new CSPS-based technology may provide a novel treatment option for rapid relief from DH (Clinicaltrials.gov NCT02937623). Clinical significanceA dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) demonstrated significantly greater dentine hypersensitivity reductions following a single application compared with no treatment. Strips were well-liked by participants and generally well tolerated. A strip containing CSPS, which dissolves within 10min, may provide rapid relief from dentine hypersensitivity.

Meta-analysis of stem cell transplantation for reflex hypersensitivity after spinal cord injury

Stem cells have been used in novel therapeutic strategies for spinal cord injury (SCI), but the effect of stem cell transplantation on neuropathic pain after SCI is unclear. The current meta-analysis evaluates the effects of stem cell transplantation on neuropathic pain after SCI. We first conducted online searches of PubMed, Web of Science, China Academic Journals Full-text Database, and Wanfang Data for randomized controlled trials that compared stem cell transplantation and vehicle treatments in rodent models of neuropathic pain after SCI. Quality assessment was performed using Cochrane Reviewer’s Handbook 5.1.0, and meta-analysis was conducted with RevMan 5.3. Then, we developed a rat model of SCI and transplanted bone marrow mesenchymal stem cells to verify meta-analysis results. Twelve randomized, controlled trials (n=354 total animals) were included in our meta-analysis and divided by subgroups, including species, timing of behavioral measurements, and transplantation time after SCI. Subgroup analysis of these 12 studies indicated that stem cell-treated animals had a higher mechanical reflex threshold than vehicle groups, with a significant difference in both rats and mice. The thermal withdrawal latency showed the same results in mouse subgroups, but not in rat subgroups. In addition, mesenchymal stem cell transplantation was an effective treatment for mechanical, but not thermal reflex hypersensitivity relief in rats. Transplantation showed a positive effect when carried out at 3 or 7days post-SCI. Stem cell transplantation alleviates mechanical reflex hypersensitivity in rats and mice and thermal reflex hypersensitivity in mice after SCI.

Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH-affected molars: an 8-week clinical study

ObjectivesThe objective of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 8 weeks combining a single in-office application and a homed-based program with desensitizing products containing 8% arginine and calcium carbonate.Materials and methodsNineteen children with at least one MIH-affected molar with hypersensitivity were included. Hypersensitivity was assessed with an evaporative (air) stimulus and a tactile stimulus. Each child received a single in-office treatment with a desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste), followed by 8 weeks of brushing twice daily with a desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride (elmex Sensitive Professional toothpaste), using the elmex Sensitive Professional toothbrush. Additionally, the corresponding mouthwash (elmex Sensitive Professional mouthwash) was used. Clinical assessments were made at baseline, immediately after the in-office treatment and after 1, 2, 4 and 8 weeks of brushing twice daily.ResultsFifty-six molars with an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were included. Application of the desensitizing paste decreased hypersensitivity significantly immediately and throughout the 8 weeks recalls (p < 0.001).ConclusionsIn conclusion, 8% arginine and calcium carbonate were able to reduce hypersensitivity successfully during this 8-week trial.Clinical relevanceHypersensitivity is a major complaint in patients with MIH. This is the first study evaluating the desensitizing effect of a desensitizing paste containing 8% arginine and calcium carbonate in patients with MIH.

Penetration of sub-micron particles into dentinal tubules using ultrasonic cavitation

ObjectivesFunctionalised silica sub-micron particles are being investigated as a method of delivering antimicrobials and remineralisation agents into dentinal tubules. However, their methods of application are not optimised, resulting in shallow penetration and aggregation. The aim of this study is to investigate the impact of cavitation occurring around ultrasonic scalers for enhancing particle penetration into dentinal tubules. MethodsDentine slices were prepared from premolar teeth. Silica sub-micron particles were prepared in water or acetone. Cavitation from an ultrasonic scaler (Satelec P5 Newtron, Acteon, France) was applied to dentine slices immersed inside the sub-micron particle solutions. Samples were imaged with scanning electron microscopy (SEM) to assess tubule occlusion and particle penetration. ResultsQualitative observations of SEM images showed some tubule occlusion. The particles could penetrate inside the tubules up to 60μm when there was no cavitation and up to ∼180μm when there was cavitation. ConclusionsThe cavitation bubbles produced from an ultrasonic scaler may be used to deliver sub-micron particles into dentine. This method has the potential to deliver such particles deeper into the dentinal tubules. Clinical significanceCavitation from a clinical ultrasonic scaler may enhance penetration of sub-micron particles into dentinal tubules. This can aid in the development of novel methods for delivering therapeutic clinical materials for hypersensitivity relief and treatment of dentinal caries.

An exploratory clinical trial to evaluate the efficacy of an experimental dentifrice formulation in the relief of dentine hypersensitivity

ObjectivesThis study aimed to investigate whether addition of an octadecene/maleic anhydride copolymer (O/MA) to a potassium nitrate (KNO3) dentifrice could facilitate delivery of potassium to dentine and enhance its efficacy in dentine hypersensitivity relief. MethodsThis was a randomised, examiner-blind, controlled, parallel group study in 139 healthy subjects with at ≥2 sensitive teeth. Assessment of dentine hypersensitivity to tactile (Yeaple probe) and evaporative (air) stimuli (Schiff Sensitivity Scale, visual analogue scale [VAS]) was carried out at baseline and after 1, 2, 4 and 8 weeks twice daily treatment with an experimental 5% KNO3/3% O/MA dentifrice, a comparator 5% KNO3 dentifrice (active comparator), a 0% KNO3/3% O/MA dentifrice (placebo) and a regular fluoride dentifrice (negative control). This study was not powered to detect statistically significant differences between treatments. ResultsAcross the treatment period an improvement in sensitivity to evaporative air stimulus was observed for all products and to a tactile stimulus for the potassium-containing treatments, with the greatest reductions for the experimental dentifrice (5% KNO3/3% O/MA). Reductions in sensitivity observed for the potassium-containing dentifrices compared to the placebo and negative control dentifrices were statistically significantly for Schiff sensitivity score and tactile threshold at all time-points and for VAS at Weeks 4 and 8. Trends in the study data also favoured the experimental dentifrice, compared to the active comparator dentifrice, for all clinical measures. Study treatments were generally well tolerated. ConclusionThis study provides initial clinical evidence to suggest that addition of a polymer excipient may enhance the anti-sensitivity efficacy of potassium-containing dentifrices. Clinical significanceDaily use potassium-containing dentifrices are established as efficacious for the relief of dentine hypersensitivity. Inclusion of a polymer excipient in such formulations may facilitate delivery of potassium to the dentine surface and so enhance clinical efficacy. Further clinical studies are required to confirm this hypothesis.

Uniquely formulated varnish for hypersensitivity relief

Uniquely formulated varnish for hypersensitivity relief

Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain.

Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question, we generated skeletal pain by injecting and confining GFP-transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy were then measured on days 21, 28, and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hind paw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors, whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that although bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive end points for clinical trials.

Influence of wedged cervical lesions and dentine hypersensitivity on quality of life

Aim. To study the influence of wedged cervical lesions and dentin hypersensitivity on quality of life. Methods. 118 patients with wedged cervical lesions and dentin hypersensitivity were examined. The quality of life was assessed using the Oral Health Impact Profile (OHIP-14) 14-item questionnaire focusing on seven dimensions of impact (functional limitation, pain, psychological discomfort, physical disability, psychological disability, social disability and handicap). Treatment in patients of the first group (57 patients) included dentin hypersensitivity relief using the «Nanoflyuor» fluoride varnish and dental restoration in patients with medium and promoted stages of wedged cervical lesions. Patients of the control group were treated with «Gluftored» fluoride liquid, dental restoration was performed in patients with medium and promoted stages of wedged cervical lesions. Results. Patients with superficial wedged cervical lesions had lower OHIP-14 scores, indicating better quality of life, with promoted wedged cervical lesions - higher OHIP-14 scores. OHIP-14 scores were higher in patients aged 31-40 and 41-50 years, and lower in patients aged 18-30 years and over 51 years. After treatment of promoted wedged cervical lesions OHIP-14 scores were better in the treatment group compared to the control group with statistically significant difference in functional limitation and physical disability dimensions scores, as well as in combined OHIP-14 score. In patients with medium-stage wedged cervical lesions there was a relevant difference in functional limitation, pain and psychological disability scores. There were no significant differences between the groups in patients with superficial wedged cervical lesions. Conclusion. Dentin hypersensitivity and bad dental appearance influence the patients’ comfort decreasing their quality of life, with minimal influence in patients with superficial wedged cervical lesions and maximal influence in patients with promoted wedged cervical lesions.

Efficacy in reducing dentine hypersensitivity of a regimen using a toothpaste containing 8% arginine and calcium carbonate, a mouthwash containing 0.8% arginine, pyrophosphate and PVM/MA copolymer and a toothbrush compared to potassium and negative control regimens: An eight-week randomized clinical trial

ObjectiveEvaluate the efficacy of three regimens integrating toothpaste, toothbrush and mouthwash in reducing dentine hypersensitivity. MethodsEight-week single-centre, three-cell, double-blind, randomized study was conducted in the Dominican Republic. Subjects entered one of the three regimens: (1) toothpaste containing 8% arginine and 1450ppm mono-fluorophosphate, in a calcium carbonate base, a soft-bristle toothbrush followed by a mouthwash containing 0.8% arginine, PVM/MA copolymer, pyrophosphates, and 0.05% sodium fluoride; (2) toothpaste containing 5% potassium nitrate and 1450ppm sodium fluoride, a soft-bristle toothbrush, followed by a mouthwash containing 0.51% potassium chloride and 230ppm sodium fluoride; and (3) toothpaste containing 1450ppm mono-fluorophosphate, a soft-bristle toothbrush followed by a fluoride/arginine free mouthwash. Tactile and Air-Blast dentine hypersensitivity measurements were performed at baseline, two, four, and eight weeks. For treatment group comparisons, ANCOVA and post hoc Tukey's pair-wise (α=0.05) were used. Kaplan–Meier survival analysis was performed to evaluate Time to Treatment Improvement. Results120 subjects were enrolled, 118 completed the study. The Tactile hypersensitivity mean scores showed statistically significant improvement at two, four and eight (p≤0.001) weeks in the arginine regime; the potassium regime did not show significant (p≥0.05) improvement. Air-Blast Hypersensitivity scores had a statistically significant decrease at two (p=0.006), four (p=0.006) and eight (p=0.002) weeks in arginine and potassium regimes (p≤0.05). The most effective treatment proved to be arginine (p≤0.05) compared to the potassium regime. ConclusionArginine regimen provided the greatest reduction in Tactile and Air-Blast dentine hypersensitivity compared to potassium and negative control regimens; and provides faster dentine hypersensitivity relief than potassium regimen.

Relief of Hypersensitivity after Nerve Injury from Systemic Donepezil Involves Spinal Cholinergic and γ-Aminobutyric Acid Mechanisms

Evoking spinal release of acetylcholine (ACh) produces antinociception in normal animals and reduces hypersensitivity after nerve injury, and some studies suggest that ACh-mediated analgesia relies on γ-aminobutyric acid (GABA)-ergic signaling in the spinal cord. In this study, the authors tested the spinal mechanisms underlying the antihypersensitivity effects of donepezil, a central nervous system-penetrating cholinesterase inhibitor, in a rat model of neuropathic pain. Male Sprague-Dawley rats were anesthetized, and L5 spinal nerve ligation was performed unilaterally. Withdrawal threshold to a paw pressure test was measured before and after intraperitoneal administration of donepezil, with or without intrathecal antagonists for cholinergic and GABAergic receptors. Microdialysis studies in the ipsilateral dorsal horn of the lumbar spinal cord were also performed to measure extracellular ACh and GABA. Donepezil increased the withdrawal threshold in spinal nerve ligation rats but not in normal rats. The antihypersensitivity effect of donepezil (1 mg/kg) in spinal nerve ligation rats was reduced by intrathecal pretreatment with atropine (30 μg), a muscarinic receptor antagonist; mecamylamine (100 μg), a nicotinic receptor antagonist; bicuculline (0.03 μg), a γ-aminobutyric acid receptor type A antagonist; and CGP 35348 (30 μg), a γ-aminobutyric acid receptor type B antagonist. ACh and GABA concentrations in the microdialysates from the spinal dorsal horn were increased after intraperitoneal donepezil treatment (1 mg/kg) in both normal and spinal nerve ligation rats. Systemic administration of donepezil reduces hypersensitivity after nerve injury by increasing extracellular ACh concentration, which itself induces GABA release in the spinal cord. Activation of this spinal cholinergic-GABAergic interaction represents a promising treatment for neuropathic pain.