The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM.

Drug repositioning promises the advantages of reducing costs and expediting approvalschedules. An induction of the anesthetic and sedative drug; midazolam (MDZ), regulatesinhibitory neurotransmitters in the vertebrate nervous system. In this study we show the potentialfor drug repositioning of MDZ for dentin regeneration. A porcine dental pulp-derived cell line(PPU-7) that we established was cultured in MDZ-only, the combination of MDZ with bonemorphogenetic protein 2, and the combination of MDZ with transforming growth factor-beta 1. Thedifferentiation of PPU-7 into odontoblasts was investigated at the cell biological and genetic level.Mineralized nodules formed in PPU-7 were characterized at the protein and crystal engineeringlevels. The MDZ-only treatment enhanced the alkaline phosphatase activity and mRNA levels ofodontoblast differentiation marker genes, and precipitated nodule formation containing a dentinspecificprotein (dentin phosphoprotein). The nodules consisted of randomly orientedhydroxyapatite nanorods and nanoparticles. The morphology, orientation, and chemicalcomposition of the hydroxyapatite crystals were similar to those of hydroxyapatite that hadtransformed from amorphous calcium phosphate nanoparticles, as well as the hydroxyapatite inhuman molar dentin. Our investigation showed that a combination of MDZ and PPU-7 cellspossesses high potential of drug repositioning for dentin regeneration.

The present study revealed that CO(2) laser radiation attenuated the late component of SEPs induced by electrical tooth stimulation, triggering the DNIC effect but with no aftereffect.

In drug repositioning research, a new concept in drug discovery and new therapeutic opportunities have been identified for existing drugs. Midazolam (MDZ) is an anesthetic inducer used for general anesthesia. Here, we demonstrate the combined effects of bone morphogenetic protein-2 (BMP-2) and MDZ on osteogenic differentiation. An immortalized mouse myoblast cell line (C2C12 cell) was cultured in the combination of BMP-2 and MDZ (BMP-2+MDZ). The differentiation and signal transduction of C2C12 cells into osteoblasts were investigated at biological, immunohistochemical, and genetic cell levels. Mineralized nodules formed in C2C12 cells were characterized at the crystal engineering level. BMP-2+MDZ treatment decreased the myotube cell formation of C2C12 cells, and enhanced alkaline phosphatase activity and expression levels of osteoblastic differentiation marker genes. The precipitated nodules consisted of randomly oriented hydroxyapatite nanorods and nanoparticles. BMP-2+MDZ treatment reduced the immunostaining for both α1 and γ2 subunits antigens on the gamma-aminobutyric acid type A (GABAA) receptor in C2C12 cells, but enhanced that for BMP signal transducers. Our investigation showed that BMP-2+MDZ has a strong ability to induce the differentiation of C2C12 cells into osteoblasts and has the potential for drug repositioning in bone regeneration.

No abstract

The aim of the this study was to investigate the combined effects of heterosegmental non-noxious and noxious stimulation on electrically induced tooth pain. The late component of somatosensory-evoked potentials (SEP), induced by electrical tooth stimulation and pain intensity, were examined under electrical stimulation to forearms. Noxious, non-noxious, and combined non-noxious and noxious electrical stimulation were applied to median nerves on the forearms. Four experimental sessions (ie, control session, combined non-noxious and noxious stimulation session, non-noxious stimulation session, and noxious stimulation session were performed for each subject at each 10-minute interval for 30 minutes. The amplitudes of the SEP and VAS scores in the combined stimulation session decreased significantly compared with those in the control session and the reduction rates were 51.1% (13.4 μV) and 41.0% (23.5 mm), respectively. These results show that the combined stimulation has a more potent analgesic effect than that of either the non-noxious or the noxious stimulation. It is suggested that a potent analgesia was produced by an activated central mechanism, including endogenous opioid and descending pain inhibitory systems due to combined non-noxious and noxious stimulation.

Although in clinical dentistry the major method used for pain relief is oral administration of analgesics, alternative methods are available, such as transcutaneous electrical nerve stimulation (TENS), acupuncture, vibration and conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory control. The aim of the present study was to investigate the combined effects of non-noxious (TENS) and noxious (CPM) stimuli on postoperative pain after extraction of an impacted wisdom tooth. The study involved 44 patients who were scheduled to undergo impacted wisdom tooth extraction. The patients were randomly allocated into four groups: noxious stimuli, non-noxious stimuli, combined noxious and non-noxious stimuli, and a sham group. On the day after tooth extraction, stimulation procedures for pain relief were performed and changes in the level of perceived pain were scored using a visual analog scale (VAS). The combination of non-noxious and noxious stimuli decreased the VAS scores by 63.7%, indicating a more potent analgesic effect than that in the non-noxious, noxious, and sham groups. This method of analgesia using a combination of nonnoxious and noxious stimuli can be applied to patients who are unable to tolerate analgesics, such as those with allergy, hypersensitivity or digestive disorders, and those who are pregnant.

We retrospectively investigated the efficacy and safety of propofol administration alone and in combination with midazolam for gag reflex suppression during dental treatment under intravenous sedation. We included 56 patients with an overactive gag reflex who were to undergo dental treatment under intravenous sedation. They were divided into propofol (P group, n = 22) and midazolam with propofol (MP group, n = 34) groups. The P group received propofol alone, while the MP group received midazolam (0.04 mg/kg) prior to target-controlled infusion (TCI) of propofol (titrated for adequate sedation). The patients' anesthetic records were evaluated for vital sign changes, adverse cardiovascular or respiratory event frequency, the number of forced treatment interruptions, and the TCI-predicted cerebral propofol concentration at gag reflex suppression (posterior tongue stimulation with a dental mirror). No significant differences were observed between the 2 groups preoperatively. There were no cases of forced interruptions or significant respiratory compromise in either group. Cardiovascular adverse event frequency was lower in the MP group than in the P group (all p < .05). Our results suggest that propofol, when combined with midazolam, minimized cardiovascular effects compared with propofol alone when used to suppress the gag reflex in patients during dental treatment under intravenous sedation.