Orexin A and B are hypothalamic peptides known to modulate arousal, feeding and reward via OX1 and OX2 receptors. Orexins are also antinociceptive in the brain but their mechanism(s) of action remain unclear. Here, we investigated the antinociceptive mechanism of orexin A in the rat ventrolateral periaqueductal gray (vlPAG), a midbrain region crucial for initiating descending pain inhibition. In vlPAG slices, orexin A (30-300 nM) depressed GABAergic evoked inhibitory postsynaptic currents (IPSCs). This effect was blocked by an OX1 (SB 334867), but not OX2 (Compound 29), antagonist. Orexin A increased the paired-pulse ratio of paired IPSCs, and decreased the frequency, but not amplitude, of miniature IPSCs. Orexin A-induced IPSC depression was mimicked by WIN 55,212-2, a cannabinoid 1 (CB1) receptor agonist. AM 251, a CB1 antagonist, reversed depressant effects by both agonists. Orexin A-induced IPSC depression was prevented by U73122 and tetrahydrolipstatin, inhibitors of phospholipase C (PLC) and diacylglycerol lipase (DAGL), respectively, and enhanced by URB602, which inhibits enzymatic degradation of 2-arachidonoylglycerol (2-AG). Moderate DAGLα, but not DAGLβ, immunoreactivity was observed in the vlPAG. Orexin A produced an overall excitatory effect on evoked postsynaptic potentials and hence increased vlPAG neuronal activity. Intra-vlPAG microinjection of orexin A reduced hot-plate nociceptive responses in rats in a manner blocked by SB 334867 and AM 251. Therefore, orexin A may produce antinociception by activating postsynaptic OX1 receptors, stimulating synthesis of 2-AG, an endocannabinoid, through a Gq-protein-mediated PLC-DAGLα enzymatic cascade culminating in retrograde inhibition of GABA release (disinhibition) in the vlPAG.

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Silicic acid produced from sodium metasilicate hydrate and metallocene polyethylene-octene elastomer (POE) were chosen as the ceramic precursor and the continuous phase, respectively, for preparation of new hybrids by an in situ sol-gel process. To obtain a better hybrid, the acrylic acid-grafted polyethylene-octene elastomer (POE-g-AA) prepared in our laboratory and used as the continuous phase was also investigated. Characterizations of POE/SiO 2 and POE-g-AA/SiO 2 composites were performed by Fourier transform infrared spectroscopy, 29 Si solid-state nuclear magnetic resonance (NMR) spectrometry, X-ray diffractometry, differential scanning calorimetry, thermogravimetry analysis, and an Instron mechanical tester. The POE-g-AA/ SiO 2 hybrid could give the positive effect on the properties of POE/SiO 2 hybrid because the carboxylic acid groups of acrylic acid should act as coordination sites for the silica phase to form chemical bonds. The result of 29 Si solid-state NMR spectra showed that Si atom coordination around SiO 4 units is predominantly Q 3 and Q 4 . Also, the POE-g-AA/SiO 2 hybrid with 15 wt % SiO 2 gave the maximum values of tensile strength and glass-transition temperature because excess particles might cause the separation between the organic and inorganic phases when the silica content was beyond this point.

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ABSTRACT:In this study, grafting of acrylic acid (AA) onto metallocene-based polyethylene-octene elastomer (POE) was investigated by using benzoyl peroxide as an initiator. Grafted product was characterized by using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction spectroscopy, and differential scanning calorimetry (DSC). Both the grafting percentage and the gel yield, at equilibrium, were higher for POE containing lower degree of comonomer content. In all cases, the crosslinking reaction was accompanied by the predominant graft reaction due to the competition of POE macroradical and excited AA. From the result of DSC and X-ray characterizations, it was found that the change of crystallinity is slight when the gel is removed from POE-g-AA copolymers. It was also proven that the effect of gel formation on the properties of the copolymer could be neglected because of the low gel yield. So, the graft method proposed in this article can produce low gel yield copolymer.