Opioid receptors have been pharmacologically classified as µ, δ, κ and ε. We have recently reported that the antinociceptive effect of morphine (a µ-opioid receptor agonist), but not that of β-endorphin (a novel µ/ε-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of µ-, δ-, κ- and ε-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60 Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52℃) tail-immersion test. Morphine and D-Ala2,N-Me-Phe4,Gly-ol-enkephalin (DAMGO), [D-Pen2-D-Pen5]enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]¬benzeneacetamide (U50,488H), and β-endorphin were tested as agonists for µ, δ, κ, and ε-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of β-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on µ- and ε¬opioid receptor agonists, we assessed pretreatment effects of β-funaltrexamine (β-FNA, a µ-opioid receptor antagonist) or β-endorphin1-27 (β-EP1-27, an ε-opioid receptor antagonist), and found that pretreatment with β-FNA significantly attenuated the antinociceptive effects of morphine and β endorphin by WBI. significantly reversed the β-EP1-27 attenuation of morphine by WBI and significantly attenuated the increased effects of β-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for µ- and ε-opioid receptors.
The aim of this study was to evaluate surface character¬istics and biological properties of the dentin -derived hydroxyapatite (HA) coating on titanium substrate. Dentin-derived HA was obtained from extracted human teeth using a calcination method at 850℃. The commercially pure titanium (cp-Ti, ASTM Grade II) was used as a metallic substrate and a radio frequency magnetron sputtering method was employed as a coating method. Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were utilized to investigate the coating aspects and composition. Atomic forced microscopy (AFM) and a surface profiler were used to assess the surface morphology and roughness. Corrosion tests were performed in phosphate- buffered saline at a 36.5 ± 1℃ in order to determine the corrosion behavior of the uncoated and coated specimens. The biocompatibility of dentin-derived HA coated specimens with fetal rat calvarial cells and human gingival fibroblasts was assessed by SEM and cell prolif¬eration analysis. The results showed that the dentin-derived HA coatings appeared to cover thinly and homogeneously the surfaces without changing of the titanium substrate. The EDX analysis of this the coating surface indicated the presence of Ca and P elements. The mean surface roughness of cp-Ti and dentin-derived coating specimens was 0.27 µm and, 1.7 µm, respectively. Corrosion tests indicated a stable passive film of the dentin-derived HA coating specimens. SEM observations of fetal rat calvarial cells and human fibroblast cells on coated surfaces showed that the cells proliferated and developed a network of dense interconnections. The cells on all specimens proliferated actively within the culture period, showing good cell viability. At day 1 and 3, dentin-derived coating specimens showed 89% and 93% cell viability, respectively, when normalized to cp-Ti specimens. These results suggest that dentin-derived HA coating using the RF magnetron sputtering method has good surface characteristics and biocompatibility.
Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in mem¬brane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above 100 µM increased malate-induced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.
During maxillofacial surgery, the infraorbital and mental nerves are blocked at eac foramen to induce local anesthesia. This study examined the relative locations of the infraorbital foramen (IOF) and mental foramen (MF) based on soft-tissue landmarks. Twenty-eight hemifacial cadavers were dissected to expose the IOF and MF. The distances between the bilateral IOFs, the bilateral MFs, the alae of the nose (alares), and the corners of the mouth (cheilions) were measured directly on cadavers by using a digital vernier caliper. The vertical and horizontal distances of the IOF and MF relative to the alare and cheilion were measured indirectly on digital photographs using Adobe Photoshop (Adobe, CA, USA). The distance between the bilateral IOFs (58.09 ± 4.04 mm) was longer than the distance between the bilateral MFs (50.32 ± 1.93 mm). The distances between the bilateral alares and cheilions were 41.22 ± 3.44 mm and 58.43 ± 6.62 mm, respectively. The IOF was located 12.92 ± 3.75 mm superior and 7.88 ± 2.56 mm lateral to the alare, and the vertical angle (Angle 1) between these structures was 31.67 ± 13.36˚ superolaterally. The MF was located 21.83 ± 3.26 mm inferior and 5.56 ± 3.37 mm medial to the cheilion, and the vertical angle (Angle 2) between these structures was 14.05 ± 10.12˚ inferomedially. In conclusion, these results provide more detailed information about the locations of the IOF and MF relative to soft-tissue landmarks.
Dlx3 and Dlx5 are homeobox domain proteins and are well-known regulators of osteoblastic differentiation. Since possible reciprocal relationships between osteogenic and adipogenic differentiation in mesenchymal stem cells exist, we examined the regulatory role of Dlx3 and Dlx5 on adipogenic differentiation using human dental pulp stem cells. Over-expression of Dlx3 and Dlx5 stimulated osteogenic differentiation but inhibited adipogenic differentiation of human dental pulp stem cells. Dlx3 and Dlx5 suppressed the expression of adipogenic marker genes such as C/EBPα, PPARγ, aP2 and lipoprotein lipase. Adipogenic stimuli suppressed the mRNA levels of Dlx3 and Dlx5, whereas osteogenic stimuli enhanced the expression of Dlx3 and Dlx5 in 3T3-L1 preadipocytes. These results suggest that Dlx3 and Dlx5 exert a stimulatory effect on osteogenic differentiation of stem cells through the inhibition of adipogenic differ¬entiation as well as direct stimulation.