Faculty Bibliography

OBJECT: The 2 aims of this study were as follows: 1) to establish outcome measures of nerve regeneration in an axolotl model of peripheral nerve injury; and 2) to define the timing and completeness of reinnervation in the axolotl following different types of sciatic nerve injury. METHODS: The sciatic nerves in 36 axolotls were exposed bilaterally in 3 groups containing 12 animals each: Group 1, left side sham, right side crush; Group 2, left side sham, right side nerve resected and proximal stump buried; and Group 3 left side cut and sutured, right side cut and sutured with tibial and peroneal divisions reversed. Outcome measures included the following: 1) an axolotl sciatic functional index (ASFI) derived from video swim analysis; 2) motor latencies; and 3) MR imaging evaluation of nerve and muscle edema. RESULTS: For crush injuries, the ASFI returned to baseline by 2 weeks, as did MR imaging parameters and motor latencies. For buried nerves, the ASFI returned to 20% below baseline by 8 weeks, with motor evoked potentials present. On MR imaging, nerve edema peaked at 3 days postintervention and gradually normalized over 12 weeks, whereas muscle denervation was present until a gradual decrease was seen between 4 and 12 weeks. For cut nerves, the ASFI returned to 20% below baseline by Week 4, where it plateaued. Motor evoked potentials were observed at 2-4 weeks, but with an increased latency until Week 6, and MR imaging analysis revealed muscle denervation for 4 weeks. CONCLUSIONS: Multiple outcome measures in which an axolotl model of peripheral nerve injury is used have been established. Based on historical controls, recovery after nerve injury appears to occur earlier and is more complete than in rodents. Further investigation using this model as a successful 'blueprint' for nerve regeneration in humans is warranted

Completion of the human genome project approximately 15 years ago was followed closely by advancements in array technology. Investigators quickly applied this new powerful tool to the genomic and proteomic study of oral squamous cell carcinoma (OSCC). Resultant publications documented chromosome, gene, mRNA, and protein alterations that characterize oral cancer. In this review, we summarize how the genomic, proteomic, and epigenetic array studies have provided insight into the process of oral carcinogenesis. We discuss the significant limitations and requirement for validation of these array studies. We also review the manner in which state-of-the-art, high-throughput approaches are being used to search for salivary and serum oral cancer biomarkers

We previously reported that endothelin A (ET-A) receptor antagonism attenuates carcinoma-induced pain in a cancer pain mouse model. In this study, we investigated the mechanism of ET-A receptor-mediated antinociception and evaluated the role of endogenous opioid analgesia. Squamous cell carcinoma (SCC) cell culture treated with the ET-A receptor antagonist (BQ-123) at 10(-6) M and 10(-5) M significantly increased production and secretion of beta-endorphin and leu-enkephalin, respectively. Behavioral studies were performed by inducing tumors in the hind paw of female nude mice with local injection of cells derived from a human oral SCC. Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days, the last day of measurement. Local administration of either naloxone methiodide (500 microg/kg), selective antagonists for mu-opioid receptor (CTOP, 500 microg/kg), or delta-opioid receptor (naltrindole, 11 mg/kg) but not kappa-opioid receptor (nor-BNI, 2.5 mg/kg) significantly reversed antinociception observed from ET-A receptor antagonism (BQ-123, 92 mg/kg) in cancer animals. These results demonstrate that antagonism of peripheral ET-A receptor attenuates carcinoma pain by modulating release of endogenous opioids to act on opioid receptors in the cancer microenvironment. PERSPECTIVE: This article proposes a novel mechanism for ET-A receptor antagonist drugs in managing cancer-induced pain. An improved understanding of the role of innate opioid analgesia in ET-A receptor-mediated antinociception might provide novel alternatives to morphine therapy for the treatment of cancer pain

Rodent pain models play an important role in understanding the mechanisms of nociception and have accelerated the search for new treatment approaches for pain. Creating an objective metric for orofacial nociception in these models presents significant technical obstacles. No animal assay accurately measures pain-induced orofacial dysfunction that is directly comparable to human orofacial dysfunction. We developed and validated a high throughput, objective, operant, nociceptive animal assay, and an instrument to perform the assay termed the dolognawmeter, for evaluation of conditions known to elicit orofacial pain in humans. Using the device our assay quantifies gnawing function in the mouse. We quantified a behavioral index of nociception and demonstrated blockade of nociception in three models of orofacial pain: (1) TMJ inflammation, (2) masticatory myositis, and (3) head and neck cancer. This assay will be useful in the study of nociceptive mediators involved in the development and progression of orofacial pain conditions and it will also provide a unique tool for development and assessment of new therapeutic approaches

PURPOSE: The purpose of the present study was to assess the safety and efficacy of oral diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) that uses ProSorb dispersion technology (Xanodyne Pharmaceuticals, Inc, licensed from AAIPharma, Wilmington, NC), to treat adult patients with acute pain after third molar extraction. PATIENTS AND METHODS: In the present multicenter, randomized, double-blind, placebo-controlled trial, patients experiencing a baseline level of pain (>/= 50 mm on a 100-mm visual analog scale within 4 hours after surgery) were randomized to receive a single dose of DPSGC at 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed for 6 hours after dosing. The efficacy endpoints included the summed pain intensity difference, total pain relief, and the median time to the onset of perceptible and meaningful pain relief (using the 2-stopwatch method). RESULTS: A total of 249 randomized patients had a significant increase in the summed pain intensity difference and total pain relief values at 3 and 6 hours across all DPSGC-treated groups compared with the placebo group (P < .0001). The onset of perceptible and meaningful pain relief was significantly faster in all DPSGC groups than in the placebo group, including the DPSGC 25-mg group (25 minutes [P = .0002] and 52 minutes [P < .0001] for perceptible and meaningful pain relief, respectively). Significantly fewer patients in the DPSGC groups required rescue medication compared with those in the placebo group (P < .0001). The global evaluation scores were significantly greater for the patients who received DPSGC than for those who received placebo (P < .0001), and more than 65% of DPSGC-treated patients rated the medication as good, very good, or excellent compared with 18% of the placebo-treated patients. DPSGC was generally well tolerated, and no serious adverse events were reported. CONCLUSIONS: The results from the present single-dose study of postoperative dental pain suggest that DPSGC offers significant pain relief compared with placebo and that the study medication provided was well tolerated by patients who required pain relief after third molar extraction

Summary form only given. This study aims to evaluate the potential of atmospheric pressure non-thermal plasma technology (NPT) to enhance the adhesive bond strength on normative dentin substrates. Two different microplasma jets were used in our experiments, a direct-current driven microhollow cathode discharge jet operated in air and a rf-driven jet operated in Ar. Other gas mixtures, e.g. He/O2 are also being explored.Initial experiments were carried out using fresh, non-carious third molars obtained under a protocol approved by the New York University College of Medicine Institutional Review Board. The occlusal enamel of each tooth was removed perpendicular to the long axis of the tooth to expose a flat dentin surface, which was subsequently polished. The specimens were randomly assigned to 3 groups for bonding and NPT applications. For the control group, three teeth were etched with phosphoric acid etched, the dentin bonding agent (DBA) was applied and the teeth were restored with a 4 mm thick resin composite. Another group of 3 teeth was treated with an Ar plasma and a third group was exposed to an air plasma. For the plasma-treated groups, the dentin substrates were etched for 15 s, rinsed for 10s and treated by the plasma for 20 s followed by DBA application and resin composite placement. All specimens were stored in water for 24 h prior to a microtensile bonding test. Preliminary data indicate that the bond strength values were not significantly affected by the Ar or air plasma treatment. We observed that teeth treated with the Ar plasma exhibited an enhanced premature failure rate (-50%) during the cutting or specimen mounting phases. This was not observed for the control or for the air plasma treated groups. Extensive surface characterization studies using various microscopy techniques, XPS, and micro-Raman are underway to assess the effect of the plasma on the surface. Optical emission spectroscopy is used to monitor the presence of reactive spe- - cies (eg. OH, O) in the plasma for various operating conditions and feed gases or gas mixtures. The results of these studies will be presented and discussed in detail at the Conference

OBJECTIVES: To compare the reliability of the disto-facial (DF) and mesio-lingual (ML) cusps of an anatomically correct zirconia (Y-TZP) crown system. The research hypotheses tested were: (1) fatigue reliability and failure mode are similar for the ML and DF cusps; (2) failure mode of one cusp does not affect the failure of the other. METHODS: The average dimensions of a mandibular first molar crown were imported into CAD software; a tooth preparation was modelled by 1.5 mm marginal high reduction of proximal walls and occlusal surface by 2.0 mm. The CAD-based tooth preparation was milled and used as a die to fabricate crowns (n=14) with porcelain veneer on a 0.5 mm Y-TZP core. Crowns were cemented on composite reproductions of the tooth preparation. The crowns were step-stress mouth motion fatigued with sliding (0.7 mm) a tungsten-carbide indenter of 6.25 mm diameter down on the inclines of either the DF or ML cusps. Use level probability Weibull curve with use stress of 200 N and the reliability for completion of a mission of 50,000 cycles at 200 N load were calculated. RESULTS: Reliability for a 200 N at 50,000 cycles mission was not different between tested cusps. SEM imaging showed large cohesive failures within the veneer for the ML and smaller for the DF. Fractures originated from the contact area regardless of the cusp loaded. CONCLUSION: No significant difference on fatigue reliability was observed between the DF compared to the ML cusp. Fracture of one cusp did not affect the other