Reduction Of Hypersensitivity Research Articles

Effectiveness of Two Desensitizer Materials, Potassium Nitrate and Fluoride Varnish in Relieving Hypersensitivity After Crown Preparation

The aim of this clinical investigation was to compare the efficacy of fluoride varnish and potassium nitrate on the reduction of hypersensitivity of prepared teeth both pre and post cementation. In this randomized clinical trial, patients who needed at least three single crowns fixed partial prosthesis were included. Two desensitizing agents including fluoride varnish and potassium nitrate were used in this study and compared to the control group (sterile saline). In each patient, each prepared tooth was randomly assigned to one group. The desensitizing agent was applied on prepared teeth immediately after tooth preparation. The sensitivity of the teeth was measured by means of an air sensitivity test based on the visual analog scale at five different time points: baseline (2 hours after preparation), 7 days after preparation, before cementation, after cementation and one-week post cementation. Data were analyzed by Kruskal-Wallis and Friedman tests with a significant level of 0.05. Overall 300 vital abutment teeth needed full crown coverage in 100 patients were included. Both desensitizers' agents decreased the sensitivity of vital abutment teeth compared to the control group at every time intervals except at baseline (p = 0.089). There was no significant difference between fluoride varnish and potassium nitrate in the reduction of pre-cementation sensitivity while one week after cementation, sensitivity was more relieved by potassium nitrate compared to fluoride varnish (p = 0.023). The application of both desensitizers is effective in sensitivity reduction of vital abutment teeth. Potassium nitrate, however, is more eligible one week after cementation compared to fluoride varnish. Both potassium nitrate and fluoride varnish are capable of desensitizing prepared tooth for the fixed partial denture.

Efficacy Comparison of Nd:YAG laser, diode laser and dentine bonding agent in dentine hypersensitivity reduction: a clinical trial.

Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli. Several modalities have been suggested for treatment of this condition such as low-level laser therapy (LLLT) and application of dentin bonding agents. The aim of this study was to compare the clinical efficacy of diode laser, Nd:YAG laser and dentin bonding agent for treatment of dentin hypersensitivity. In this study, 135 teeth of 22 patients diagnosed with dentin hypersensitivity were divided into three groups: In group 1, the teeth were irradiated by diode laser with 810 nm wavelength for 30 seconds and in group 2, the teeth were irradiated by Nd:YAG laser with 1064 nm wavelength for 40 seconds. CLEARFIL SE BOND was applied on teeth in group 3. LLLT was carried out in 3 sessions with 7-day intervals between sessions, during a period of 3 consecutive weeks. Hypersensitivity was assessed by cold test according to the criteria proposed by Uchida at baseline, immediately after treatment and at 1, 3 and 6 months, postoperatively. Reduction of dentin hypersensitivity was observed at 3 and 6 months following the use of Nd:YAG laser (p < 0.001). Reduction in dentin hypersensitivity was observed immediately after treatment in all groups. Statistically significant differences in level of dentin hypersensitivity were found between groups at 3 and at 6 months (p ≤ 0.001). The reduction in dentin hypersensitivity by Nd:YAG laser was significantly superior to that in other groups at this time. The efficacy of Nd:YAG laser in reduction of dentin hypersensitivity was significantly superior to that of other modalities at 3 and 6 months.

Stimulating muscarinic M1 receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats

Cholinergic systems modulate synaptic transmission across the neuraxis and play an important role in higher brain function including cognition, arousal and nociception. The anterior cingulate cortex (ACC) is a fundamental brain region for nociception and chronic pain, and receives cholinergic projections mainly from basal forebrain. Recently, we found that the activation of muscarinic M1 receptors in the ACC produced antinociceptive behavior in response to mechanical stimulation. However, it has not been tested whether stimulating muscarinic receptors in the ACC can reduce mechanical hypersensitivity in animal models of chronic pain.Here, we tested whether the activation of muscarinic M1 receptors in the ACC can alleviate mechanical hypersensitivity in a nerve injury model. The activation of muscarinic M1/M4 receptors by McN-A-343 injected into the contralateral side of the ACC, but not into the ventral posterolateral nucleus, was found to dose-dependently reduce mechanical hypersensitivity 7 days following partial sciatic nerve ligation in rats. The reduction of mechanical hypersensitivity by McN-A-343, was blocked by a selective muscarinic M1 antagonist, but not a M4 receptor antagonist. Importantly, the nerve injury model did not change the protein expression of muscarinic M1 receptors in the ACC. Additionally, a type A γ-aminobutyric acid (GABAA) receptor agonist injected into the ACC reduced the mechanical hypersensitivity in this injury model. Finally, a GABAA receptor antagonist blocked the reduction of mechanical hypersensitivity by McN-A-343 in the injury model. Collectively, these results suggest that activations of muscarinic M1 receptors in the ACC reduce nerve injury-induced mechanical hypersensitivity through GABAergic transmission via GABAA receptors.

The Assessment of the Effectiveness of Remineralization and Laser Therapy in Cervical Dentine Hypersensitivity

The aim of study was to compare the clinical effectiveness of 810nm laser therapy, remineralising therapy with MI PASTE PLUS� (GC), and toothbrush with Sensodyne� Repair&amp;Protect (GSK) in cervical dentine hypersensitivity. The study was performed on 60 subjects (34 females, 24 males), with at least one tooth affected by cervical dentine hypersensitivity. The patients were randomly divided in three study groups (20 subjects for each group), related to the type of desensitizing therapy: 810nm laser therapy, remineralising therapy with gel MI PASTE PLUS�, toothbrushing with Sensodyne� Repair&amp;Protect). The assessment of the therapy effectiveness was performed by analysis of Schiff Cold Air Sensitivity Scale, with scores directly related to the level of dentine hypersensitivity. For laser group the scores decreased from 2.25 at baseline, at 1.35 at 3 days, and 0.2 at 7 days, with significant statistical differences at 3 days, and 7 days comparing with baseline. For MI PASTE PLUS� (GC) study group the scores decreased from 2.20 at baseline, at 1.60 at 3 days, and 1.30 at 7 days, with significant statistical differences at 3 days, and 7 days comparing with baseline. For Sensodyne� Repair&amp;Protect (GSK) study group the scores decreased from 2.15 at baseline, at 1.90 at 3 days, and 1.45 at 7 days, with significant statistical differences at 3 days, and 7 days comparing with baseline. Low level laser therapy showed better reduction in cervical hypersensitivity, followed by the therapy using MI PASTE PLUS� (GC) gel, and by the toothbrush with Sensodyne� Repair&amp;Protect (GSK) toothpaste.

Treatment of single maxillary gingival recession associated with non-carious cervical lesion: Randomized clinical trial comparing connective tissue graft alone to graft plus partial restoration.

Gingival recession (GR) is frequently associated with non-carious cervical lesion (NCCL) forming a combined defect (CD). The aim of this study was to evaluate a new multidisciplinary protocol for CDs. Forty patients presenting 40 Miller's Class I or II GR defects associated with B+ tooth cervical defect were randomly allocated to one of the following treatments: test group (n=20), partial restoration (PR) of the NCCL, in which the apical border of the restoration was placed 1mm beyond the cement-enamel junction estimation, and connective tissue graft (CTG+PR) and Control Group (n=20), odontoplasty of the NCCL and connective tissue graft (CTG). Clinical, aesthetic and patient-centred outcomes were evaluated. After 12months, CD coverage rates were 75.3% (2.5±1.0mm) for CTG+PR and 74.6% (2.4±1.1mm) for CTG (p>0.05). The estimated complete root coverage was 60% (n=12) for CTG+PR and 70% (n=14) for CTG. CTG+PR resulted in significantly better dentin hypersensitivity (DH) reduction (p=0.034). Both groups resulted in aesthetic improvements; however, the CTG+PR group showed better gingival contour results. CTG and CTG+PR were effective to treat CD. Use of PR resulted in better gingival margin contour and DH reduction, without effect on CD coverage by CTG. (NCT02817763).

Does enamel matrix derivative application improve clinical outcomes after semilunar flap surgery? A randomized clinical trial.

To evaluate the treatment of gingival recessions by semilunar coronally positioned flap plus enamel matrix derivative (SCPF + EMD). Thirty patients with class I localized gingival recession were included. They were randomly allocated in two groups: SCPF + EMD and SCPF. Recession height (RH), recession width (RW), width of keratinized tissue (WKT), thickness of keratinized tissue (TKT), probing depth (PD), and clinical attachment level (CAL) were measured at baseline, 6 and 12months post-surgery. Patient/professional evaluation of esthetics and root sensitivity was performed. After 12months, mean root coverage was 1.98 ± 0.33mm for SCPF + EMD (90.86 ± 14.69%) and 1.85 ± 0.41mm (79.76 ± 17.44%) for SCPF (p > 0.05). The esthetic evaluation by the patient showed preference for SCPF + EMD. According to the professional evaluation (QCE), the use of EMD decreases the appearance of postoperative scar tissue line. There was a significant reduction in root hypersensitivity with no further complaints by the patients. The addition of EMD provides significantly better esthetics to SCPF, according to patient and professional assessments. SCPF + EMD is effective but not superior to SCPF for root coverage, after 12months. Previous clinical trials showed that the combination of EMD with coronally advanced flaps may enhance the outcome of root coverage. There is a lack of studies testing the combination of EMD with SCPF. The combination SCPF + EMD provides better esthetics when compared to the SCPF and is effective, but not superior, to SCPF for root coverage, after 12months. NCT02459704.

Nanoemulsion adjuvant–driven redirection of TH2 immunity inhibits allergic reactions in murine models of peanut allergy

Immunotherapy for food allergies involves progressive increased exposures to food that result in desensitization to food allergens in some subjects but not tolerance to the food. Therefore new approaches to suppress allergic immunity to food are necessary. Previously, we demonstrated that intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal antibody and TH17-polarized immunity, as well as systemic TH1-biased cellular immunity with suppression of pre-existing TH2-biased immunity. We hypothesized that immunization with food in conjunction with the nanoemulsion adjuvantcould lead to modulation of allergic reactions in food allergy by altering pre-existing allergic immunity and enhancing mucosal immunity. Mice were sensitized to peanut with aluminum hydroxide or cholera toxin. The animals were then administered 3 monthly intranasal immunizations with peanut in the nanoemulsion adjuvant or saline. Mice were then challenged with peanut to examine allergen reactivity. The NE intranasal immunizations resulted in marked decreases in TH2 cytokine, IgG1, and IgE levels, whereas TH1 and mucosal TH17 immune responses were increased. After allergen challenge, these mice showed significant reductions in allergic hypersensitivity. Additionally, the NE immunizations significantly increased antigen-specific IL-10 production and regulatory T-cell counts, and the protection induced by NE was dependent in part on IL-10. Control animals immunized with intranasal peanut in saline had no modulation of their allergic response. NE adjuvant-mediated induction of mucosal TH17 and systemic TH1-biased immunity can suppress TH2-mediated allergy through multiple mechanisms and protect against anaphylaxis. These results suggest the potential therapeutic utility of this approach in the setting of food allergy.

Fluoride varnish versus glutaraldehyde for hypersensitive teeth: a randomized controlled trial, meta-analysis and trial sequential analysis

Reports indicate Gluma and Duraphat are commonly used in-office agents to treat hypersensitive teeth. Considering this, the aim of this paper is to compare Gluma and Duraphat using a randomized controlled trial, meta-analysis collating evidences from previous studies and trial sequential analysis. Thirty-eight participants were randomized. Hypersensitivity and visual analog scale (VAS) scores were recorded at baseline, 5min and 7days. Oral health-related quality of life (OHIP) questionnaire was administered at baseline and 7days. Statistical analysis was performed to identify significant differences between the variables. For the meta-analysis, electronic data bases were searched and eligible data was extracted and analysed using RevMan 5.0. Trial sequential analysis was performed using O'Brien-Fleming boundary approach for the primary outcome. Both agents caused significant reduction in hypersensitivity and VAS score at 5min and 7days in the randomized trial with no superiority. The quality of life significantly improved in patients treated with both the agents. Four studies including the present trial in meta-analysis and trial sequential analysis indicated that Gluma produced significant reduction in VAS scores at 7days. Gluma produces significant reduction in hypersensitivity at 7days post treatment compared with Duraphat. There is definite lack of evidence on the long-term effect of these agents. This paper provides strong evidence on the use of Gluma for hypersensitive teeth. This also is a way forward to future research on long-term effects, adverse effects and cost-effectiveness studies.

Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents.

Intraoperative hypothermia and postoperative pain control are two important clinical challenges in anesthesiology. Transient receptor potential vanilloid 1 has been implicated both in thermoregulation and pain. Transient receptor potential vanilloid 1 antagonists were not advanced as analgesics in humans in part due to a side effect of hyperthermia. This study tested the hypothesis that a single, preincision injection of a transient receptor potential vanilloid 1 antagonist could prevent anesthesia-induced hypothermia and decrease the opioid requirement for postsurgical hypersensitivity. General anesthesia was induced in rats and mice with either isoflurane or ketamine, and animals were treated with transient receptor potential vanilloid 1 antagonists (AMG 517 or ABT-102). The core body temperature and oxygen consumption were monitored during anesthesia and the postanesthesia period. The effect of preincision AMG 517 on morphine-induced reversal of postincision hyperalgesia was evaluated in rats. AMG 517 and ABT-102 dose-dependently prevented general anesthesia-induced hypothermia (mean ± SD; from 1.5° ± 0.1°C to 0.1° ± 0.1°C decrease; P < 0.001) without causing hyperthermia in the postanesthesia phase. Isoflurane-induced hypothermia was prevented by AMG 517 in wild-type but not in transient receptor potential vanilloid 1 knockout mice (n = 7 to 11 per group). The prevention of anesthesia-induced hypothermia by AMG 517 involved activation of brown fat thermogenesis with a possible contribution from changes in vasomotor tone. A single preincision dose of AMG 517 decreased the morphine dose requirement for the reduction of postincision thermal (12.6 ± 3.0 vs. 15.6 ± 1.0 s) and mechanical (6.8 ± 3.0 vs. 9.5 ± 3.0 g) withdrawal latencies. These studies demonstrate that transient receptor potential vanilloid 1 antagonists prevent anesthesia-induced hypothermia and decrease opioid dose requirements for the reduction of postincisional hypersensitivity in rodents.

Efficacy of Milk as a Desensitizing Agent for the Treatment of Sensitivity Following Scaling and Root Planing.

Background:Dentine hypersensitivity (DH) is the most common problem encountered by most of the dentists in their day-to-day clinical practice. It is characterized by a sharp pain or discomfort arising as a response to thermal, chemical, or osmotic stimuli and is caused due to exposure of dentine after the enamel or cementum at the root surface has been lost by the treatment, underlying dental and gingival diseases or physiologic wear and tear of the teeth. This further complicates preventive oral hygiene procedures by the patients, which jeopardize periodontal treatment or may as well aid in periodontal treatment failure.Aim and Objective:To evaluate the efficacy of commercially available milk as a desensitizing agent for the treatment of sensitivity following scaling and root planing.Materials and Methods:Patients were selected randomly for scaling and then assessed for sensitivity. Those patients having DH were divided into two groups, wherein the Group A (test) patients were advised to rinse with commercially available milk at room temperature and those in Group B (control) with a commercially available mouthwash (Sentosil-SF). A four-point verbal rating scale was designed to record the numerical value of DH and were recalled for follow-up on 4th, 7th, and 10th day posttreatment.Results:The study demonstrated that there was a considerable reduction in hypersensitivity in both the groups on the 7th and 10th day. In the milk group, eight patients showed a complete reduction in hypersensitivity on 7th day and 13 patients on 10th day, while in the mouthwash group, five patients showed the same on 7th day and ten patients on the 10th day, thus suggesting that more individuals in the milk group were benefited. However, there was no statistically significant difference between the groups in every visit.Conclusion:Although there is a vast literature available which suggests the efficacy of commercially available mouthwash in reducing hypersensitivity, this study is the first of its kind which evaluates the efficacy of commercially available milk in reducing sensitivity which is induced postscaling. Considering that milk rinse is cheap and easily available at home, it can be used as a desensitizing agent, and rinsing with milk for few days is effective and stable in quick reduction of hypersensitivity induced by scaling.

Propofol produces preventive analgesia via GluN2B-containing NMDA Receptor/ERK1/2 Signaling Pathway in a rat model of inflammatory pain.

Propofol, an intravenous anesthetic, has been shown to offer superior analgesic effect clinically. Whether propofol has preventive analgesic property remains unexplored. The present study investigated the antinociceptive effect of propofol and underlying molecular and cellular mechanisms via pre-emptive administration in a formalin-induced inflammatory pain model in rats. Male adult Sprague–Dawley rats were randomly allocated into four groups: naïve (Group Naïve), formalin injection only (Group Formalin), and formalin injection at 30 min (Group P-30 min) or 2 h (Group P-2 h) after intravenous infusion of propofol (0.6 mg kg−1 min−1) for 1 h. Nociceptive responses and protein expression of phosphorylated- or pan-GluN2B, ERK1/2, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase in the spinal dorsal horn were evaluated. Alteration of intracellular Ca2+ concentration induced by N-methyl-D-aspartate (NMDA) receptor agonists with or without pre-treatment of propofol was measured using fluorometry in SH-SY5Y cells while neuronal activation in the spinal dorsal horn by immunofluorescence. Pre-emptive propofol reduced pain with a delayed response to formalin and a reduction in hypersensitivity that lasted at least for 2 h. The formalin-induced activation of spinal GluN2B and ERK1/2 but not p38 or c-Jun N-terminal kinase was also diminished by propofol treatment. Preconditioning treatment with 3 µM and 10 µM of propofol inhibited Ca2+ influx mediated through NMDA receptors in SH-SY5Y cells. Propofol also reduced the neuronal expression of c-Fos and p-ERK induced by formalin. This study shows that pre-emptive administration of propofol produces preventive analgesic effects on inflammatory pain through regulating neuronal GluN2B-containing NMDA receptor and ERK1/2 pathway in the spinal dorsal horn.

Intrathecal administration of AYX2 DNA-decoy produces a long-term pain treatment in rat models of chronic pain by inhibiting the KLF6, KLF9 and KLF15 transcription factors.

BackgroundNociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive von Frey testing.ResultsResults demonstrated that a one-time administration of decoys binding to the Kruppel-like transcription factors (KLFs) 6, 9, and 15 produces a significant and weeks–month long reduction in mechanical hypersensitivity compared to controls. In the spared nerve injury model, decoy efficacy was correlated to its capacity to bind KLF15 and KLF9 at a specific ratio, while in the chronic constriction injury model, efficacy was correlated to the combined binding capacity to KLF6 and KLF9. AYX2, an 18-bp DNA decoy binding KLF6, KLF9, and KLF15, was optimized for clinical development, and it demonstrated significant efficacy in these models.ConclusionsThese data highlight KLF6, KLF9, and KLF15 as transcription factors required for the maintenance of chronic pain and illustrate the potential therapeutic benefits of AYX2 for the treatment of chronic pain.

Neural manual vs. robotic assisted mobilization to improve motion and reduce pain hypersensitivity in hand osteoarthritis: study protocol for a randomized controlled trial.

[Purpose] The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of neural manual vs. robotic assisted on pain in sensitivity as well as analyse the quantitative and qualitative movement of hand in subjects with hand osteoarthritis. [Subjects and Methods] Seventy-two patients, aged 50 to 90 years old of both genders, with a diagnosis of hand Osteoarthritis (OA), will be recruited. Two groups of 36 participants will receive an experimental intervention (neurodynamic mobilization intervention plus exercise) or a control intervention (robotic assisted passive mobilization plus exercise) for 12 sessions over 4 weeks. Assessment points will be at baseline, end of therapy, and 1 and 3 months after end of therapy. The outcomes of this intervention will be pain and determine the central pain processing mechanisms. [Result] Not applicable. [Conclusion] If there is a reduction in pain hypersensitivity in hand OA patients it can suggest that supraspinal pain-inhibitory areas, including the periaqueductal gray matter, can be stimulated by joint mobilization.

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.

Efficacy of a bioactive material and nanostructured desensitizing on dentin hypersensitivity treatment

Abstract Introduction Dentin hypersensitivity is a frequent occurrence in dental practice. It is clinically characterized by acute, short, and temporary pain in response to mechanical, chemical, thermal, or osmotic stimuli resulting from dentin exposure. Objective To compare in vivo the effect of an experimental crystalline bioactive material and nanostructured desensitizing on the pain assessment among patients with cervical dentin hypersensitivity. Material and method Thirty patients were selected for this study, who were randomly assigned to two groups (n=15) in a split-mouth design. Each patient received two treatments: group 1 (fluoride gel and bioactive material) and group 2 (fluoride gel and nanostructured desensitizing). Pain analyses were performed using a visual analogue scale, ranging 0-10. Baseline pain measurement was performed prior to initial treatment (T0) and new measurements were carried out weekly for 3 weeks (T1, T2, and T3) before materials were reapplied. Final pain analysis was performed 3 months after initial treatment (T4). Degree of pain reduction was calculated using the formula T0 - Tperiod after treatment. The data of the pain measurements were analyzed using 2-way repeated measure ANOVA and Tukey’s test (α=0.05). Result Regardless of evaluation period, there was no statistical difference on pain reduction between the treatments (p&gt;0.05). The degree of pain was reduced significantly in each evaluated period for all tested treatments (p&lt;0.05), by approximately three degrees after 3 months. Conclusion The tested desensitizing materials were effective on dentin hypersensitivity reduction.

Analgesic Effect of Recombinant GABAergic Cells in a Model of Peripheral Neuropathic Pain

Chronic neuropathic pain represents a clinically challenging state with a poor response to current treatment options. Long-term management of chronic pain is often associated with the development of tolerance, addiction, and other side effects, reducing the therapeutic value of treatment. Alternative strategies based on cell therapy and gene manipulation, balancing the inhibitory and excitatory events in the spinal cord, may provide sustained pain relief in the long term. Transplantation of GABAergic cells has been successfully used to enhance inhibition and to restore physiological spinal pain processing. However, since the underlying mechanism of chronic pain development involves changes in several pain-signaling pathways, it is essential to develop an approach that targets several components of pain signaling. Recombinant cell therapy offers the possibility to deliver additional analgesic substances to the restricted area in the nervous system. The current study explores the analgesic potential of genetically modified rat embryonic GABAergic cells releasing a peptidergic NMDA receptor antagonist, Serine(1)-histogranin (SHG). Overactivation of glutamate NMDA receptors contributes to the hyperexcitability of spinal neurons observed in chronic pain models. Our approach allows us to simultaneously target spinal hyperexcitability and reduced inhibitory processes. Transplantable cells were transduced by viral vectors encoding either one or six copies of SHG cDNAs. The analgesic potential of recombinant cells after their intraspinal transplantation was evaluated in a model of peripheral nerve injury. Enhanced reduction of hypersensitivity to thermal and mechanical stimuli was observed in animals treated by recombinant cells compared to the nonrecombinant group. The recombinant peptide was detected in the spinal tissue, suggesting its successful production by transplanted cells. Our results demonstrate the feasibility of using recombinant cells releasing adjunct analgesic peptides in the therapy of neuropathic pain.

Clinical Efficacy of Fluoride Varnish and Low-Level Laser Radiation in Treating Dentin Hypersensitivity.

The objective of this study was to compare the efficacy of fluoride varnish (Fluorniz(r)) and irradiation with a gallium-arsenide-aluminum diode laser in the treatment of cervical dentin hypersensitivity. Cervical dentin hypersensitivity (CDH) is a painful condition that is highly prevalent in the world's adult population, with one in six patients presenting this symptom. Eighty-six teeth were divided into two groups: Group 1, teeth treated with Fluorniz; Group 2, teeth irradiated with a GaAlAs laser at a 4 J/cm2 dose. The two treatments were applied to the buccal cervical region in four sessions, at intervals of 72 to 96 h. The response of the patient to tactile and thermal-evaporative stimuli was rated on a visual analog scale. The results showed a reduction of hypersensitivity in response to tactile and thermal-evaporative stimulation at the end of treatment in both groups. In conclusion, short-term treatment with Fluorniz was found to be more effective than low-level laser radiation in reducing cervical dentin hypersensitivity.

Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials.

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (−89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (−81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner.

(406) AYX2 transcription factor decoy produces a long-term resolution of chronic pain following a single intrathecal injection by inhibiting the triumvirate of KLF6, 9 and 15 transcription factors

Chronic pain limits activity and current treatments often contribute to further reduced function, limiting their chronic usage and creating a large unmet medical need. AYX2 is a drug candidate developed specifically to interrupt the maintenance and allow the resolution of chronic pain following a single or limited number of intrathecal administrations. Chronic pain is maintained through well-orchestrated waves of gene regulation across a wide range of gene categories within the dorsal root ganglia – spinal cord network. Transcription factors control gene expression and constitute a promising class of targets for transformative pharmacological interventions. Transcription factor decoys are powerful inhibitors of transcription factor activity. A series of decoys were designed against 35 complementary transcription factors or family of transcription factors to identify targets capable of producing a large and sustained resolution of chronic pain. These decoys were subjected to an in vivo - in vitro based attrition process and revealed that a one-time inhibition of the triumvirate of Kruppel-like transcription factors (KLF) 6, 9 and 15 produced a large reduction of mechanical hypersensitivity that was maintained until it resolved in control animals. The effect was observed in the spared nerve injury, chronic constriction injury and tibio-tarsal mono-arthritis models of chronic pain. Across pain states, the efficacy of a decoy relied either on its KLF15/KLF9 binding ratio or on the combined binding capacity to KLF6 and KLF9. AYX2 is an 18-bp long decoy that combines these complementary KLF6, 9 and 15 binding features and is optimized for clinical development. This work identifies KLF6, 9 and 15 as essential transcription factors for the maintenance of chronic pain. It further illustrates the potential clinical therapeutic benefits of AYX2 for producing a robust and long-term resolution of chronic pain states from multiple etiologies. This work is supported by Adynxx, Inc. Chronic pain limits activity and current treatments often contribute to further reduced function, limiting their chronic usage and creating a large unmet medical need. AYX2 is a drug candidate developed specifically to interrupt the maintenance and allow the resolution of chronic pain following a single or limited number of intrathecal administrations. Chronic pain is maintained through well-orchestrated waves of gene regulation across a wide range of gene categories within the dorsal root ganglia – spinal cord network. Transcription factors control gene expression and constitute a promising class of targets for transformative pharmacological interventions. Transcription factor decoys are powerful inhibitors of transcription factor activity. A series of decoys were designed against 35 complementary transcription factors or family of transcription factors to identify targets capable of producing a large and sustained resolution of chronic pain. These decoys were subjected to an in vivo - in vitro based attrition process and revealed that a one-time inhibition of the triumvirate of Kruppel-like transcription factors (KLF) 6, 9 and 15 produced a large reduction of mechanical hypersensitivity that was maintained until it resolved in control animals. The effect was observed in the spared nerve injury, chronic constriction injury and tibio-tarsal mono-arthritis models of chronic pain. Across pain states, the efficacy of a decoy relied either on its KLF15/KLF9 binding ratio or on the combined binding capacity to KLF6 and KLF9. AYX2 is an 18-bp long decoy that combines these complementary KLF6, 9 and 15 binding features and is optimized for clinical development. This work identifies KLF6, 9 and 15 as essential transcription factors for the maintenance of chronic pain. It further illustrates the potential clinical therapeutic benefits of AYX2 for producing a robust and long-term resolution of chronic pain states from multiple etiologies. This work is supported by Adynxx, Inc.

Clinical evaluation of the efficacy of one self-adhesive composite in dental hypersensitivity.

The aim of the present study was to investigate the clinical effectiveness over 12weeks of Vertise Flow(™), a self-adhering composite, in dental hypersensitivity (DH). The study was conducted as a split-mouth randomized clinical trial. Vertise Flow™ was compared to the following: (1) Universal Dentine Sealant, (2) Clearfil Protect Bond, and (3) Flor-Opal® Varnish. A total of 46 patients with 116 hypersensitive teeth were studied. Pain experience was generated by a cold stimulus and assessed using the visual analog scale (VAS) of pain. The response was recorded before the application of the materials (pre-1), immediately after (post-1), at 1- (post-2), 2- (post-3), and 12-week controls (post-4). Statistical differences in VAS were performed using the Kruskal-Wallis analysis at the different time-points (P < 0.05), adjusting statistical significances for multiple comparisons (Bonferroni correction). All the materials showed any statistically significant differences at the baseline. After the application of each material, a VAS decrease was demonstrated at every post-control. VF showed significant hypersensitivity reduction in post-1. Statistically significant relief was also observed in post-2 while no significant differences were detected in post-3 and post-4. After 12-week controls, there was no statistically significant hypersensitivity reduction using VF in respect to the other materials. On the other hand, any significant differences were detected in the decrease of the VAS irrespective of the desensitizing agent employed at the 12-week controls. The significant increase in VAS scores within the 12-weeks of environment suggested there is instability of VF when used as desensitizing agent.