Reduction Of Hypersensitivity Research Articles

Local and systemic photobiomodulation using a 650nm LED on skin temperature and hyperalgesia in cellulite: a randomized, placebo-controlled and double-blinded clinical trial.

Cellulite is a skin condition that significantly affects women, characterized by "holes" or depressions in the skin, affecting approximately 95% of women at some point in their lives. Cellulite often presents inflammatory symptoms such as increased skin temperature and hyperalgesia. Photobiomodulation, whether applied locally or systemically, has demonstrated important anti-inflammatory effects in various conditions. This study investigates the effects of local and systemic photobiomodulation on hip culottes temperature increases and hyperalgesia in patients with grades 2 to 4 cellulite. Cellulite assessment was carried out using detailed anamnesis, photographic records, algometry, and infrared thermography. Participants received randomized bilateral treatment with or without systemic irradiation using LED photobiomodulation on the hip culottes for four weeks, three times a week. This study aimed to evaluate the effect of photobiomodulation, especially locally applied, together or not with systemic irradiation, on cellulite hyperalgesia and skin temperature among 25 female participants. The group that received only LED treatment showed an increase in pain threshold of 8% and 20% on the right and left sides, respectively, while the group treated with LED + ILIB showed an increase in pain threshold of 32% on both sides. Local photobiomodulation produced a skin temperature decrease of 0.4°C, while the combination of local and systemic irradiation produced an average skin temperature decrease of 1.2°C. Our results clearly demonstrate a significantly beneficial effect of LED therapy for cellulite treatment, especially when administered in combination with mILIB, leading to a significant reduction of pain hypersensitivity and skin temperature, indicating a regional subcutaneous improvement of the inflammatory status.

NANOTECHNOLOGY IN DENTISTRY: DIAGNOSTICS AND TREATMENT

The rapid development of nanotechnology in medicine and dentistry has led to an exponential increase in the scope of research in this area. Aspects of nanotechnology that have already brought benefits include advanced drug delivery platforms, molecular imaging, and the development of treatment materials in dental practice. The aim of the research. To investigate the current possibilities of using nanotechnology in dentistry for diagnosis and treatment. Materials and methods of the research. The materials were used scientific publications by authors conducting their scientific and practical research in the field of dentistry and nanotechnology. The search was conducted in the scientometric databases PubMed, Scopus, Web of Science, Google Scholar using the terms “nanoparticles”, “oral cavity”, “nanomaterials”, “nanodentistry”, “diseases”, “biomaterials”, “treatment”, “diagnostics”. The research was conducted using such scientific methods as theoretical generalization and grouping, formalization, analysis, synthesis, and generalization of the results. The search resulted in the selection of publications for the period 2019-2024 that studied nanotechnology and its application in dental practice in diagnosis and treatment and will be discussed in this review. Results. The article shows a unique feature of nanotechnology, which is that the properties of a material at the nanoscale can differ from those at the macro level. This can be explained by two reasons: first, nanomaterials have a large surface area to volume ratio, which causes their high reactivity and, accordingly, affects their mechanical and electrical properties. Secondly, at the nanoscale, quantum effects dominate the material's behavior, giving rise to interesting observations of its electromagnetic and optical properties. Knowing the beneficial aspects of nanomedicine, scientists are trying to use nanotechnology to diagnose, treat and prevent dental diseases. Nanotechnology is used for sensitive medical procedures. They also demonstrate successful and useful applications for precise pain management, tooth restoration, and reduction of tooth hypersensitivity. Nanomaterials can plug open dentinal tubules, improving patient comfort and overall oral health. Orthodontic therapy has also been revolutionized by nanomaterials with shape memory properties, which enables faster and more efficient tooth movement. The development of revolutionary products and therapeutic alternatives is supported by ongoing research efforts, enabling the creation of dental implants, fillings and prostheses that closely mimic the characteristics of natural teeth. Nano-delivery systems are being developed to deliver drugs precisely into the oral cavity, providing optimal therapeutic outcomes with minimal side effects. This review highlights the multifaceted aspects of nanomedicine and how nanotechnology is proving to be useful in the diagnosis and treatment of dental diseases. The integration of nanotechnology into dentistry represents a groundbreaking evolution that goes beyond conventional oral care methods, allowing for the development of innovative diagnostic methods and improved oral health. Prospects for further research. Nanotechnology has revolutionized dentistry by changing the way oral care is conceptualized, delivered, and maintained. To develop effective methods for the diagnosis and treatment of dental diseases, it is necessary to continue research on the optimization of the mechanical properties and cytotoxicity of dental composite materials based on nanotechnology.

TRMT1L-catalyzed m2 2G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.

tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and Nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA, as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing m2 2G solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of acp3U and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA levels, coinciding with a reduction in global translation rates and hypersensitivity to oxidative stress. Our results establish TRMT1L as the elusive methyltransferase catalyzing the m2 2G27 modification on tRNA Tyr, resolving a long-standing gap of knowledge and highlighting its potential role in a tRNA modification circuit crucial for translation regulation and stress response.

Desensitization treatment in MIH-affected teeth: a systematic review.

The present systematic review aims to summarize the current evidence regarding various treatment modalities and their results when dealing with hypersensitivity in teeth with Molar-Incisor Hypomineralization (MIH). Systematic searches were conducted in PubMed and Scopus using the search terms "MIH AND Hypersensitivity AND treatment." Studies involving children aged 6-18years diagnosed with MIH and exhibiting hypersensitivity were considered for inclusion. The outcomes examined included clinical, behavioral, and psychosocial treatment options for reducing hypersensitivity. A meta-analysis was performed for six of the included articles, and the I2 value was calculated to determine heterogeneity. A total of eight articles met the inclusion criteria for this review, with six eligible for the meta-analysis. Various treatment modalities, such as dental mousse, sealing, laser therapy, and crown therapy, demonstrated significant reductions in hypersensitivity individually (p < 0.05). The treatment methods that offer the most effective reduction in hypersensitivity are sealing with resin composite or glass ionomer cement for mild cases of MIH, while crown therapy is more effective for severe cases of MIH. However, the small number of participants and short follow-up times limit the strength of these conclusions.

VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model

BackgroundPituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and is considered a promising new migraine drug target. Although intravenous PACAP triggers migraine attacks and a recent phase II trial with a PACAP-inhibiting antibody showed efficacy in migraine prevention, targeting the PACAP receptor PAC1 alone has been unsuccessful. The present study investigated the role of three PACAP receptors (PAC1, VPAC1 and VPAC2) in inducing migraine-relevant hypersensitivity in mice.MethodsHindpaw hypersensitivity was induced by repeated PACAP38 injections. Tactile sensitivity responses were quantified using von Frey filaments in three knockout (KO) mouse strains, each lacking one of the PACAP-receptors (Ntotal = 160). Additionally, ex vivo wire myography was used to assess vasoactivity of the carotid artery, and gene expression of PACAP receptors was examined by qPCR.ResultsPACAP38 induced hypersensitivity in WT controls (p < 0.01) that was diminished in VPAC1 and VPAC2 KO mice (p < 0.05). In contrast, PAC1 KO mice showed similar responses to WT controls (p > 0.05). Myograph experiments supported these findings showing diminished vasoactivity in VPAC1 and VPAC2 KO mice. We found no upregulation of the non-modified PACAP receptors in KO mice.ConclusionsThis study assessed all three PACAP receptors in a migraine mouse model and suggests a significant role of VPAC receptors in migraine pathophysiology. The lack of hypersensitivity reduction in PAC1 KO mice suggests the involvement of other PACAP receptors or compensatory mechanisms. The results indicate that targeting only individual PACAP receptors may not be an effective migraine treatment.

A Comparative Study on the Safety and Efficacy of Erbium Laser Therapy Versus Traditional Treatments in Managing Dentin Hypersensitivity: An Observational Study.

Background This study aimed to explore the potential efficacy and safety of laser therapy compared with traditional desensitizing treatments in the management of dentin hypersensitivity. Methodology A comprehensive observational study was conducted on 138 adult individuals aged 18-65 diagnosed with dentin hypersensitivity. Participants were allocated to either the laser therapy or traditional treatment group. The laser therapy group received treatment using the Fotona LightWalker® Erbium laser at 2,940 nm. The energy density was set at 20 J/cm² using continuous and contact modes, with the laser tip held perpendicularly to the irradiated site. Each session lasted five minutes, conducted bi-weekly for three months. Traditional treatment included the in-office application of 5% sodium fluoride varnish application once every 15 days for three months and the use of desensitizing toothpaste as part of regular oral hygiene routines. Follow-up assessments were conducted 6 and 12 months post-treatment to evaluate the longevity and stability of the treatment effects. Primary outcomes were assessed by dentin hypersensitivity reduction measured using Visual Analog Scale (VAS) scores and tactile hypersensitivity assessments. Results Laser therapy consistently surpassed traditional treatment in reducing dentin hypersensitivity, as reflected by the significantly lower VAS scores. Notably, at 3, 6, and 12 months, laser therapy demonstrated mean VAS scores of 2.5 (±1.5), 1.2 (±0.9), and 0.6 (±0.5), respectively, while the traditional treatment group exhibited higher scores (3.8 ± 1.2, 4.5 ± 1.0, and 4.0 ± 0.7, respectively). Statistical analysis revealed that these differences were highly significant (p < 0.001). Tactile hypersensitivity assessments echoed these findings, with laser therapy consistently maintaining lower scores (0.8 ± 0.7 at 6 months, 0.4 ± 0.3 at 12 months) compared to traditional treatment (3.5 ± 1.0 at 6 months, 4.0 ± 0.7 at 12 months) with statistical significance at all time points (p < 0.001). Conclusions Although this study lacks a randomized controlled design, the observed substantial reduction in VAS scores and tactile hypersensitivity assessments, along with the favorable safety profile of laser therapy, suggest its potential as an effective alternative for managing dentin hypersensitivity.

The impact of transcutaneous electrical acustimulation (TEA) on rectal distension-induced pain in patients with irritable bowel syndrome (IBS)-A study to determine the optimal TEA delivery modalities and effects on rectal sensation and autonomic function.

Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function. Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment. Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04). TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

The effectiveness of calcium hydroxylapatite-based Implant in eliminating increased sensitivity of teeth

BACKGROUND: Dental hypersensitivity affects up to 57% of the world’s population. In Russia, high demand for treating hyperesthesia was found among patients aged 30–59 years. Despite the large number of studies conducted, understanding of the etiology and proposed treatment methods to eliminate increased sensitivity of teeth, there is still no effective drug to treat this pathology. Current methods do not ensure long-term elimination of hypersensitivity, which substantiates the need to develop new treatment methods. AIM: To determine the effectiveness of the Radiesse implant (Merz North America, USA) in patients with dental hyperesthesia. MATERIALS AND METHODS: Eighty-six patients aged 35–44 years — men and women with dental hyperesthesia — were examined. The condition of periodontal tissues of teeth with hypersensitivity was assessed by clinical examination methods, and an objective assessment of dental hypersensitivity (tactile impact — TV) was carried out using an electromagnetic device Yeaple Probe (XininX Research Inc., USA). RESULTS: Dental hypersensitivity after a single injection of the Radiesse implant steadily decreases compared to its initial values. CONCLUSIONS: Dental hypersensitivity after a single injection of the Radiesse implant steadily decreases compared to its initial values (p 0.05). Effective reduction of dental hypersensitivity when using Radiesse (Merz North America, USA) lasts for more than 6 months in contrast to the effect of standard treatments.

Antagonistic functions of CTL1 and SUH1 mediate cell wall assembly in Arabidopsis.

Plant genomes contain numerous genes encoding chitinase-like (CTL) proteins, which have a similar protein structure to chitinase belonging to the glycoside hydrolase (GH) family but lack the chitinolytic activity to cleave the β-1,4-glycosidic bond in chitins, polymers of N-acetylglucosamine. CTL1 mutations found in rice and Arabidopsis have caused pleiotropic developmental defects, including altered cell wall composition and decreased abiotic stress tolerance, likely due to reduced cellulose content. In this study, we identified suppressor of hot2 1 (suh1) as a genetic suppressor of the ctl1 hot2-1 mutation in Arabidopsis. The mutation in SUH1 restored almost all examined ctl1 hot2-1 defects to nearly wild-type levels or at least partially. SUH1 encodes a Golgi-located type II membrane protein with glycosyltransferase (GT) activity, and its mutations lead to a reduction in cellulose content and hypersensitivity to cellulose biosynthesis inhibitors, although to a lesser extent than ctl1 hot2-1 mutation. The SUH1 promoter fused with the GUS reporter gene exhibited GUS activity in interfascicular fibers and xylem in stems; meanwhile, the ctl1 hot2-1 mutation significantly increased this activity. Our findings provide genetic and molecular evidence that the antagonistic activities of CTL1 and SUH1 play an essential role in assembling the cell wall in Arabidopsis.

Effect of Iontophoresis on the Effectiveness of Nano-Hydroxyapatite and Pro-argin in In-Office Treatment of Dentin Hypersensitivity: A Split-Mouth Randomized Clinical Trial.

Background and objectives Dentin hypersensitivity (DH) treatment is one of the main challenges dentists facein their daily clinical practice. Current therapies provide only temporary relief and require multiple applications to exhibit results, and there is a lack of evidence related to the long-term effects of these agents. Nano-hydroxyapatite (n-HA) and pro-argin (8.0% arginine-calcium carbonate) have recently been used fordentin desensitization with a one-time in-office application, but the effects are interim. However, a standard treatment protocol demandsdefinitive or enduring results. Since iontophoresis amplifiesthe transportof neutral and ionized drugsacross a membrane, the use of these desensitizing agents with iontophoresis may be beneficial to accomplish satisfactory results.This study was conducted to evaluate whether iontophoresis could enable better penetration of nano-hydroxyapatite and pro-argin into the dentin, enhancing and prolonging their therapeutic effect. Materials and methods Forty-five participants with dentin hypersensitivity in the age group of 20 to 60 years were included. In each individual, four teeth with cervical lesions (one from each quadrant) were selected and divided randomly into four groups: group I: desensitizing paste containing nano-hydroxyapatite, group II: desensitizing paste containing nano-hydroxyapatite with iontophoresis, group III: desensitizing paste containing pro-argin, and group IV: desensitizing paste containing pro-argin with iontophoresis; followed by one-time application of the agents. Sensitivity was assessed by tactile, air blast, and cold-graded thermal tests(CGTTs) before and immediately after application, after one week, and at the end of the first, third, and sixth months. Statistical analysis Statistical analysis was done by repeated measures ANOVA for within-group comparison. Intergroup comparison was done using one-way ANOVA and Tukey's post-hoc test. Results All the groups showed a statistically significant reduction in dentin hypersensitivity (p<0.001). The reduction inhypersensitivity in various groups can be graded as group II (3.578/1.800/1.556) > group IV (3.367/1.755/1.555) > group I (2.3781/1.022/0.822) > group III (2.222/0.911/0.778) as evaluated by tactile, air blast, and cold-graded thermal tests, respectively. Group II and group IV presented a significant reduction in sensitivity levels consistent for up to six months. Conclusion Nano-hydroxyapatite and pro-argin can be used effectively for reducing dentin hypersensitivity. Iontophoresis can be a valuable adjunct for their improved delivery, enhancing and prolonging their effectiveness.

The Effect of STW5 (Iberogast) on Reflux Symptoms in Patients With Concurrent Dyspeptic Symptoms: A Double-blind Randomized Placebo-controlled Crossover Trial.

It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

Efficacy of Diode Laser 940 nm in Dentine Hypersensitivity Reduction: A Clinical Trial

Background: Dentin hypersensitivity is a discomfort arising from unprotected dentin as a response to heat, cold, touch, or pressure stimuli. Various treatment modalities, including laser light, have been used to manage such a problem. This study aims to evaluate the efficacy of diode laser 940 nm, with different powers in managing dentin hypersensitivity. Materials and Methods: A cross-sectional study was conducted from 1 January–5 April 2023 on a cohort of patients presented to the dental department clinics of our college with dentine hyper-sensitivity. A 10-second continuous mode diode laser light 940 nm at two different powers was used to evaluate its desensitizing effect for managing dentin hypersensitivity for six patients with a total number of teeth treated, 38 teeth. A jet of air/water was applied for a specific period and a certain distance from the tooth surface. Scores were documented for evaluating responses using the VAS scale. Results: A statistically significant decrease in dentine hypersensitivity was found immediately after one treatment session and after a 14-day follow-up period. Conclusions: It was established that using a diode laser (940 nm) successfully resolved instant and longstanding dentin hypersensitivity pain.

Sida cordifolia L. attenuates behavioral hypersensitivity by interfering with KIF17-NR2B signaling in rat model of neuropathic pain

Ethnopharmacological relevanceSida cordifolia L., a perennial subshrub belonging to the Malvaceae family, holds noteworthy significance in the Indian Ayurvedic System and global texts. Roots of this plant are reported to be useful in neurodegenerative disorders, facial paralysis, and treating several neuropathic pain conditions such as neuralgia, and sciatica. However, despite these claims, there remains a dearth of experimental evidence showcasing the effectiveness of Sida cordifolia L. roots in mitigating neuropathic pain. Aim of the studyThe primary objective of this study was to assess the analgesic properties of the whole extract (SCE) obtained from the roots of Sida cordifolia L., as well as its aqueous fraction (SAF) in rat model of chronic constriction injury (CCI)-induced neuropathic pain. Furthermore, in-depth phytochemical and molecular biology studies were conducted to identify the potential phytoconstituents and unveil the underlying mechanisms of action. Material and methodsDCM: Methanol (1:1) was used to extract the roots of Sida cordifolia L. to get whole extract (SCE) and was subjected to phytochemical investigations including LC-MS analysis. Analgesic potential of SCE was evaluated in chronic constriction injury (CCI) model of neuropathic pain in rats followed by its bioactivity guided fractionation using in-vitro anti-inflammatory assay and assessment of most potent fraction (SAF) in in-vivo pain model. We have also performed the detailed phytochemical and molecular biology investigations to delineate the mechanism of action of Sida cordifolia root extract. ResultsChronic constriction injury leads to significant decrease in paw withdrawal threshold and paw withdrawal latency indicating development of hypersensitivity in rodents. Treatment with SCE and its most potent aqueous fraction (SAF) leads to significant and dose-dependent reduction in pain-like behavior of nerve injured rats. Pro-inflammatory cytokines (TNF-α, IL-1β), glia cell markers (Iba1, ICAM1), neuropeptides (CGRP and Substance P), KIF-17 and NR2B expressions were found to be significantly upregulated in DRG and spinal cord of nerve injured rats. Treatment with SCE and SAF suppressed oxido-inflammatory cascade along with attenuation of KIF-17 mediated NR2B trafficking and neuroinflammation in DRG and spinal tissues of neuropathic rats. HPTLC and HR-MS analysis suggest betaine as major constituent in SAF which along with other phytoconstituents. ConclusionsBoth the whole extract (SCE) and the aqueous fraction (SAF) demonstrate a significant reduction in mechanical and thermal hypersensitivity by inhibiting KIF-17 mediated NR2B signaling in nerve injured rats and may be used as a potential alternative for the treatment of chronic pain. Our findings support the use of roots of Sida cordifolia L. in neuropathic pain conditions as acclaimed by its traditional use.

Rapid Generation and Molecular Docking Analysis of Single-Chain Fragment Variable (scFv) Antibody Selected by Ribosome Display Targeting Cholecystokinin B Receptor (CCK-BR) for Reduction of Chronic Neuropathic Pain.

A robust cell-free platform technology, ribosome display in combination with cloning, expression, and purification was utilized to develop single chain Fragment variable (scFv) antibody variants as pain therapy directed at the mouse cholecystokinin B (CCK-B) receptor. Three effective CCK-B peptide-specific scFvs were generated through ribosomal display technology. Soluble expression and ELISA analysis showed that one antibody, scFv77-2 had the highest binding and could be purified from bacterial cells in large quantities. Octet measurements further revealed that the CCK-B scFv77-2 antibody had binding kinetics of KD = 1.794 × 10-8 M. Molecular modeling and docking analyses suggested that the scFv77-2 antibody shaped a proper cavity to embed the whole CCK-B peptide molecule and that a steady-state complex was formed relying on intermolecular forces, including hydrogen bonding, electrostatic force, and hydrophobic interactions. Thus, the scFv antibody can be applied for mechanistic intermolecular interactions and functional in vivo studies of CCK-BR. The high affinity scFv77-2 antibody showed good efficacy with binding to CCK-BR tested in a chronic pain model. In vivo studies validated the efficacy of the CCK-B receptor (CCK-BR) scFv77-2 antibody as a potential therapy for chronic trigeminal nerve injury-induced pain. Mice were given a single dose of the CCK-B receptor (CCK-BR) scFv antibody 3 weeks after induction of a chronic trigeminal neuropathic pain model, during the transition from acute to chronic pain. The long-term effectiveness for the reduction of mechanical hypersensitivity was evident, persisting for months. The anxiety- and depression-related behaviors typically accompanying persisting hypersensitivity subsequently never developed in the mice given CCK-BR scFv. The effectiveness of the antibody is the basis for further development of the lead CCK-BR scFv as a promising non-opioid therapeutic for chronic pain and the long-term reduction of chronic pain- and anxiety-related behaviors.

Root coverage surgery for dentin hypersensitivity reduction: a systematic review and meta-analysis of randomized controlled trials.

To evaluate the effectiveness of root coverage surgery in reducing dentin hypersensitivity (DH) through a systematic review and meta-analysis. Unrestricted search of four indexed databases up to September 2022 was performed to identify randomized controlled trials (RCTs) evaluating the effect of root coverage surgery on DH frequency and/or intensity presurgically (baseline) and at least 3 months postsurgically. Two authors independently conducted study screening and data extraction. Subgroup meta-analyses were performed separately for stimulated and unstimulated DH frequency and intensity at different timepoints. The risk of bias and quality of the available evidence were assessed. Nineteen RCTs presenting data from 7 days to 30 months after root coverage surgery with various treatment modalities were included from the 662 identified studies. A total of 486 patients contributed 784 recession defects. Results from the subgroup meta-analyses showed that, overall, root coverage surgery reduced the risk for DH by 67% (RR, 0.33; 95% CI, 0.21 to 0.53) and 53% (RR, 0.47; 95% CI, 0.38 to 0.58) upon unstimulated and stimulated DH assessment, respectively. The DH intensity was also significantly reduced (mean visual analog score difference, 2.37; 95% CI, 2.02 to 2.71) upon stimulated DH assessment. No significant changes in DH intensity were observed upon unstimulated DH assessment. The included studies did not have high risk of bias and the quality of evidence was low to high. Existing evidence suggests that root coverage surgery may effectively reduce the DH frequency and intensity.

PEG-asparaginase treatmentregimens for acute lymphoblastic leukaemia in children: a network meta-analysis.

PEG-asparaginase treatmentregimens for acute lymphoblastic leukaemia in children: a network meta-analysis.

RNA-Seq Reveals Sex Differences in Gene Expression during Peripheral Neuropathic Inflammation and in Pain Relief from a COX-2 Inhibiting Theranostic Nanoemulsion.

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of activating transcription factor 3 (Atf3), however, only the female DRG shows decreased expression following drug treatment. Alternatively, S100A8 and S100A9 expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.

Amorphous Calcium Magnesium Fluoride Phosphate—Novel Material for Mineralization in Preventive Dentistry

This paper describes novel and innovative amorphous calcium magnesium fluoride phosphate (ACMFP) core-shell microparticles that may be applied in preventive dentistry for the prevention of caries and the treatment of dentin hypersensitivity. The particles can be synthesized with varied fluoride content, up to approximately 6 wt%, without any observable differences in morphology or crystallinity. Fluoride release from the particles is correlated to the fluoride content, and the particles are readily converted to fluoride-substituted hydroxyapatite or fluorapatite in a simulated saliva solution. The remineralization and dentin tubule occlusion potential of the particles was evaluated in vitro on acid-etched dentin specimens, and treatment with the ACMFP particles resulted in complete tubule occlusion and the formation of a dense mineralization layer. The acid resistance of the mineralization layer was improved compared to treatment with analogous particles without fluoride inclusion. A cross-sectional evaluation of dentin specimens after treatment revealed the formation of high aspect ratio fluorapatite crystals and poorly crystalline hydroxyapatite, respectively. The particles of the current study provide a single source vehicle of readily available calcium, phosphate, and fluoride ions for the potential remineralization of carious lesions as well as exposed dentin tubules for the reduction of hypersensitivity.

KATP Channel Prodrugs Reduce Inflammatory and Neuropathic Hypersensitivity, Morphine-Induced Hypersensitivity, and Precipitated Withdrawal in Mice.

Previous studies show ATP-sensitive potassium (KATP) channel openers can reduce hypersensitivity associated with chronic pain models in rodents, and reduce morphine tolerance. Many agonists of KATP channels are not soluble in physiologically relevant vehicles, requiring adaptation for clinical use. This study compared the antinociceptive activity of novel KATP channel targeting prodrugs, CKLP1, CKLP2, and CF3-CKLP. These prodrugs are activated by endogenous alkaline phosphatase enzymes present in the peripheral and central nervous systems. Analgesic capabilities of intrathecally injected prodrugs were tested in rodent models of spinal nerve ligation (SNL) and complete Freund's adjuvant (CFA) as models for neuropathic and inflammatory pain, respectively. CKLP1 and CKLP2 significantly increased mechanical paw withdrawal thresholds 1-2 hours after intrathecal administration in the SNL model, but all three prodrugs were able to attenuate hypersensitivity up to 7 days after CFA treatment. The reduction of opioid tolerance and opioid-induced hypersensitivity in mice treated chronically with morphine was significantly reduced in CKLP1 and CKLP2 treated animals. Prodrug cleavage was confirmed in mouse spinal cords using liquid chromatography. These studies may aid in the further development of KATP channel prodrugs for use in treatments of chronic pain, opioid tolerance, and withdrawal. SIGNIFICANCE STATEMENT: The cromakalim prodrugs, CKLP1, CKLP2, and CF3-CKLP1 reduced hypersensitivity in inflammatory and neuropathic pain models in male and female mice. CKLP1 and CKLP2 also reduced morphine-induced hypersensitivity in a mouse model of chronic morphine exposure. CKLP2 reduced jumping and rearing behaviors after naloxone-induced precipitated morphine withdrawal. Taken together, CKLP2 demonstrates the potential for development as a non-opioid analgesic drug.

Combined non-psychoactive Cannabis components cannabidiol and β-caryophyllene reduce chronic pain via CB1 interaction in a rat spinal cord injury model.

The most frequently reported use of medical marijuana is for pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (THC) causes significant side effects. Cannabidiol (CBD) and β-caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory pain. We evaluated the analgesic potential of CBD and BCP individually and in combination in a rat spinal cord injury (SCI) clip compression chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for cold hypersensitivity in both sexes and additive effects for tactile hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced morphine-seeking behavior in a conditioned place preference (CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI pain.