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STUDY DESIGN.: Immunohistological analysis of spinal glial cells and analysis of pain behavior in the rat neuropathic pain model were investigated to clarify the function of tumor necrosis factor (TNF)-[alpha] receptors p55 type 1 and p75 type 2. OBJECTIVE.: Our objective was to investigate changes in hyperalgesia and glial cell activation after injection of antibodies to each TNF receptor in a rat sciatic nerve injury model. SUMMARY OF BACKGROUND DATA.: Recent research has revealed that activation of spinal glia plays an important role in radicular and neuropathic pain. TNF-[alpha] is reportedly a modulator for glial cell activation; however, the precise relationship between TNF-[alpha] and its 2 receptors on glial cells has not been fully delineated. METHODS.: Chronic constriction sciatic nerve injury and sham-operated rats were used. Antibodies to p55 or p75 or saline were intrathecally injected at the L5 level into rats with chronic constriction injury. Mechanical allodynia was examined for 2 weeks. Spinal cords were removed for immunohistochemical studies of ionized calcium-binding adaptor molecule 1 or glial fibrillary acidic protein. RESULTS.: Saline rats showed significantly more mechanical allodynia and the number of ionized calcium-binding adaptor molecule 1-immunoreactive microglia and glial fibrillary acidic protein-immunoreactive astrocytes were significantly increased in the saline rats compared with sham-operated rats during the 2 weeks. Injection of both antibodies significantly reduced pain behavior and anti-p55 caused significantly greater reduction compared with anti-p75. The numbers of microglia in both the antibodies groups were significantly decreased when compared with the saline group. In addition, the anti-p55 antibody suppressed microglial activation more than the anti-p75 antibody. CONCLUSION.: These results indicate that the microglial TNF-[alpha] p55 pathway played a more important role than the TNF-[alpha] p75 pathway in the pathogenesis of peripheral nerve injury pain. This suggests that future studies seeking to clarify neuropathic pain should target TNF-[alpha] and p55 receptors in microglia. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Animal model of intravertebral disc (IVD) degeneration. OBJECTIVE.: To examine production of inflammatory mediators in IVDs and neuropeptides in dorsal root ganglia (DRGs) in rat models of IVD compression and injury. SUMMARY OF BACKGROUND DATA.: Sensory nerve fibers in IVDs and inflammatory mediator responses have been verified in animal models of IVD injury. However, the IVD injury in animals incompletely models degenerated human IVDs causing discogenic low back pain, because human IVDs are also subject to compression. METHODS.: Experimental groups (controls, IVD injury, IVD compression, and their combination) of Sprague Dawley rats were prepared. Fluoro-Gold (FG; Fluorochrome, Denver, CO) was applied into coccygeal IVDs. Inflammatory mediators in IVDs, including nerve growth factor, tumor necrosis factor [alpha], interleukin 1[beta], and interleukin 6, were quantified using enzyme-linked immunosorbent assays. DRGs were immunostained for calcitonin gene-related peptide, activating transcription factor 3, and growth-associated phosphoprotein 43. RESULTS.: The upregulation of inflammatory mediators was transient in the IVD injury group but delayed and long-lasting in the IVD compression group. When the IVD injury and compression were combined, the upregulation of inflammatory mediators was long-lasting through 8 weeks. The proportion of calcitonin gene-related peptide-immunoreactive neurons among Fluoro-Gold-labeled neurons remained significantly higher in the IVD injury, compression, and combination groups than in the controls. In contrast, increases in the proportions of activating transcription factor 3-immunoreactive or growth-associated phosphoprotein 43-immunoreactive neurons in the IVD injury group animals were transient but long-lasting in the compression and combination groups compared with controls. CONCLUSION.: Disc injury in rats produces persistent increases in neuropeptides in DRGs but only transient increases in inflammatory mediators in IVDs. On the contrary, disc compression in rats produces a long-lasting increase in inflammatory mediators in IVDs and neuropeptides in DRGs. Moreover, disc compression induces persistent nerve injury and regeneration of the afferent fibers innervating IVDs. [ABSTRACT FROM AUTHOR]

In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70-36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Immunohistological analysis in an injured intervertebral disk (IVD) model. OBJECTIVE.: To elucidate and compare in rats the behavior of the sensory nervous system and inflammatory mediators in experimentally injured IVDs. SUMMARY OF BACKGROUND DATA.: Multiple human and animal studies have verified the presence of sensory nerve fibers in IVDs or investigated the behavior of inflammatory mediators in injured IVDs, but no in vivo study to date has examined the relationship between the 2. METHODS.: Eight-week-old female rats were used. In the disk-injured group, L5/L6 disks were injured with a 24-gauge needle; simultaneously, the neurotracer Fluoro-gold was injected into the L5/L6 IVD. The L5/L6 IVD dorsal root ganglia (DRGs) from the L1 to L6 levels, and the spinal cord was resected at several time points after surgery. Nerve growth factor, tumor necrosis factor (TNF)-[alpha] and interleukin (IL)-6 production in the IVDs were quantified using enzyme-linked immunosorbent assay. DRGs were immunostained for calcitonin gene-related peptide, and spinal cord sections were immunostained for ionized calcium-binding adaptor molecule-1 and glial fibrillary acidic protein. RESULTS.: Nerve growth factor, and TNF-[alpha] levels (through 1 week) and IL-6 levels (through 4 days) were significantly higher in the disk-injured group than in the noninjured group (P < 0.05). However, starting at 2 weeks (nerve growth factor and TNF-[alpha]) or 1 week (IL-6), the differences in inflammatory mediator levels between the 2 groups no longer were significant. In contrast, the percentage of calcitonin gene-related peptide-immunoreactive neurons among Fluoro-gold-labeled DRG neurons, and the numbers of ionized calcium-binding adaptor molecule-1-immunoreactive microglia and glial fibrillary acidic protein-immunoreactive astrocytes in the spinal dorsal horn remained significantly higher in the injured group than in the noninjured group at all-time points (P < 0.05). CONCLUSION.: Disk injury in rats produces persistent increases in neuropeptides in DRGs and glia in the spinal cord, but only transient increases in inflammatory mediators in IVDs. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Gait analysis and immunohistological analysis in a rat model of myofascial inflammation in low back. OBJECTIVE.: To investigate gait in a rat model of myofascial inflammation using the CatWalk gait analysis system. SUMMARY OF BACKGROUND DATA.: There are few reports examining low back pain behavior in animal models. The CatWalk is a computer-assisted gait analysis system that provides an automated way to assess gait function and this behavior during pain. METHODS.: In a myofascial inflammation group, 0.5 mL of 4% paraformaldehyde buffer and 0.5 mL of 5% Fluoro-Gold (FG) buffer were injected into bilateral multifidus muscles of rats. In a control group, FG buffer alone was injected. Five days after surgery, the gait of rats in both groups was investigated using the CatWalk system. In the present study a total of 36 gait parameters were quantified and used to judge pain-related behavior. Bilateral dorsal root ganglia (DRGs) from L1 to L6 levels were resected, and immunostained for calcitonin gene-related peptide (CGRP). RESULTS.: In the myofascial inflammation group, the mean duty cycle (duration of paw contact divided by time between consecutive paw contacts) of each paws (front and hind) were significantly higher and mean stride length (the distance between successive placements of the same paw) of each paws were significantly shorter compared with the control group. Furthermore, mean minimum contact intensity of the complete paw and mean contact intensity of each paws in the myofascial inflammation group were significantly higher compared with the control group. The proportion of CGRP-immunoreactive FG-labeled neurons among all FG-labeled DRG neurons in the myofascial inflammation group was significantly higher than the proportion in the control group. CONCLUSION.: These results suggest that myofascial inflammation in low back caused the changes to the rat's gait, including long stands, short stride, and strong paw contact. [ABSTRACT FROM AUTHOR]

New in-vivo calibration phantoms (anthropometric phantoms) were developed to meet the needs for Japanese standard phantoms. Two important characteristics of these phantoms were that (1) they were designed using Japanese body size survey data, and (2) they were designed so that they can be adapted to various positions or geometries. The performance of these phantoms was tested with respect to body size, activity distribution along the axis, and counting efficiency. The actual dimensions of the anthropometric phantoms were compared with the survey data. Most items (31 of 47) indicated good agreement between the actual values and the survey data for the adult anthropometric phantom. The activity distribution for the anthropometric phantoms was compared with that for block phantoms that simulate a uniform activity distribution. The anthropometric phantoms have some gaps in their joints. The measurement results, however, indicated that these gaps did not significantly affect the overall accuracy of the measurements. Differences in counting efficiency between the block phantoms and the anthropometric phantoms for the same age were no more than 6%. [ABSTRACT FROM AUTHOR]

Summary We evaluated the relation between dose and response for the neuroprotective effect of propofol in a rat model with incomplete cerebral ischaemia. For clarification of the mechanism of neuroprotection, plasma catechÍolamines and tumour necrosis factor-α levels were measured. Three doses (low, moderate and high-dose) of propofol were tested. These produced, respectively, a low amplitude, slowing and a burst-suppression pattern of electroencephalographic activity. Incomplete cerebral ischaemia was produced by right carotid artery occlusion combined with haemorrhagic hypotension (35 mmHg) for 30 min. Neurological outcome at 72 h post-ischaemia in the high-dose group was significantly better than that in both low-dose and moderate-dose groups. Propofol exhibited a trend in the dose-related attenuation of the increases in plasma adrenaline and noradrenaline during ischaemia. Tumour necrosis factor-α increased during and after ischaemia in all groups with no intergroup differences. The results indicate that a burst-suppression dose of propofol provides neuroprotection. The protective effect can not be completely explained by the attenuating effect on circulating catecholamines. [ABSTRACT FROM AUTHOR]