Lysophosphatidic acid receptor (LPA(1)) signaling initiates neuropathic pain through demyelination of the dorsal root (DR). Although LPA is found to cause down-regulation of myelin proteins underlying demyelination, the detailed mechanism remains to be determined. In the present study, we found that a single intrathecal injection of LPA evoked a dose- and time-dependent down-regulation of myelin-associated glycoprotein (MAG) in the DR through LPA(1) receptor. A similar event was also observed in ex vivo DR cultures. Interestingly, LPA-induced down-regulation of MAG was significantly inhibited by calpain inhibitors (calpain inhibitor X, E-64 and E-64d) and LPA markedly induced calpain activation in the DR. The pre-treatment with calpain inhibitors attenuated LPA-induced neuropathic pain behaviors such as hyperalgesia and allodynia. Moreover, we found that sciatic nerve injury activates calpain activity in the DR in a LPA(1) receptor-dependent manner. The E-64d treatments significantly blocked nerve injury-induced MAG down-regulation and neuropathic pain. However, there was no significant calpain activation in the DR by complete Freund's adjuvant treatment, and E-64d failed to show anti-hyperalgesic effects in this inflammation model. The present study provides strong evidence that LPA-induced calpain activation plays a crucial role in the manifestation of neuropathic pain through MAG down-regulation in the DR.
Background: Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results: In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient ( Lpar1 −/− ) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin ( atx +/− ), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx +/− or Lpar1 −/− mice. Conclusions: These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain.
The effects of applied stress and cold work on the hydrogen embrittlement of iron have been examined by constant load tests under cathodic charging.The results obtained are summerized as follows.(1) Hydrogen embrittlement of the annealed iron specimen was induced by applying a stress higher than the yield one. This result indicates that the mobile dislocations play an important role for hydrogen embrittlement of annealed iron.(2) With the prestrained iron specimen, hydrogen embrittlement occurred even at an applied stress less than the yield one. This result means that the dislocations induced by preplastic deformation play an important role for hydrogen embrittlement of prestrained iron.(3) The quasi-cleavage fracture which was characterized by petal-like pattern was recognized on both annealed and prestrained iron. In this case, the average diameter of facets decreased with increasing prestrain. On the other hand, the density of facets increased with increasing prestrain. It is suggested that the inclusions and the dense regions of dislocations contribute to the susceptible nucleus for hydrogen cracking.
A three-dimensional finite element proqram is developed for calculating thermal stress in bulk single crystals during Czochralski growth. Elastic anisotropy is taken into account in this program. Thermal stress analyses of a GaAs bulk single crystal are performed in the cases of [001] and [111] pulling directions using its temperature distribution obtained from a heat conduction analysis and its material properties. The stress component and the parameter representing dislocation density are compared between the anisotropic analysis taking account of elastic anisotropy and the isotropic analysis using the Young's modulus and the Poisson's ratio in the {111} plane. Significant differences are found in their values and distribution patterns between both analyses.
We have deposited stainless steel films onto glass slides under various ion bombardment conditions by dc unbalanced magnetron sputtering. The apparatus was equipped with an external coil around the magnetron cathode which allows us to alter the ion flux to the substrate.A commercial SUS304 steel disk (φ50 mm×2 mm) was used as a target. The sputtering gas was Ar (99.999%) and its pressure ranged from 0.2 to 1.0 Pa. The applied dc power and external coil current were also varied in the range Pdc=100∼220 W and Ic=−3∼4 A, respectively. The crystal structure, composition, internal stress, corrosion resistance and hardness of deposited films were examined.The deposited films showed bcc structure with strong (110) preferred orientation. The film surface looks like martensite with very fine grain. The Cr composition in deposited films appeared to decrease about 2 mass% compared to target material. The ion bombardment showed very small effect on the structure and the composition of deposited films. The corrosion resistance and the hardness of the films seemed to be much better than bulk material.
The aim of our study is to develop a conventional method to estimate a fatigue life of textile composite based on damage propagation analysis. The textile composite is treated as heterogeneous bodies with anisotropy for fiber bundles and isotropy for matrix, respectively. The stress distribution in unit cell model of textile is estimated by FEM and damage in each element is evaluated. At the same time, material properties of each element under cyclic loading are estimated from fatigue test results carried out for UD composite. The proposed method is applied to the plain woven CFRP and it is confirmed that the proposed method is applicable to estimation of fatigue life of textile composites. Moreover, it is revealed that the fatigue life distributions are also estimated by considering the scatter of fatigue strength of UD composite.
