Antinociceptive effects of gentiopicroside on neuropathic pain induced by chronic constriction injury in mice: a behavioral and electrophysiological study.

Gentiopicroside (Gent) is promising as an important protective secoiridoid compound against pain. The present study was designed to investigate whether administration of Gent would alleviate the expression of nociceptive behaviors and whether it would cause the relevant electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in mice. Gent was administered from the seventh day after surgery for 8 consecutive days. Behavioral parameters and sciatic functional index were assessed immediately before surgery and on days 7, 8, 10, 12, and 14 post-CCI, and electrophysiological activities of sciatic nerve were recorded immediately after the behavioral test on the last day. The present study has shown that administration of Gent (at a dose of 50 and 100 mg/kg) increased behavioral parameters from day 8 compared with the CCI-NS group. Electrophysiological data indicated that CCI caused a significant reduction in nerve conduction velocities in the sciatic nerves and the amplitudes of compound action potential, while Gent at a dose of 50 or 100 mg/kg caused a significant recovery of electrophysiological changes induced by CCI. Our data indicated that Gent has antinociceptive effects on neuropathic pain induced by CCI.

Oxysophocarpine Ameliorates Carrageenan-induced Inflammatory Pain via Inhibiting Expressions of Prostaglandin E2 and Cytokines in Mice.

Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6.

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway.

OBJECTIVE: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. METHODS: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in the spinal cord (L4/5) were analyzed by using Western blot. RESULTS: Administration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1ß at the dose of 80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10mg/kg (i.p.). CONCLUSION: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

Optimal FSH usage in revascularization of allotransplanted ovarian tissue in mice.

BACKGROUD: Ovarian transplantation is a useful method for preserving the fertility of young women with cancer who undergo radiotherapy and chemotherapy. Follicle-stimulating hormone (FSH) is use to protect transplanted ovarian tissues from ischemia injury through promoting revascularization after transplantation, but the side effect of high level FSH is ovarian overstimulation leading to substantial follicular loss. In this study, we investigated the optimal usage of FSH on revascularization in the in vitro cultured ovarian tissues before and after transplantation. RESULTS: FSH mainly exhibited an additive response in the gene and protein expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and follicle stimulating hormone receptor (FSHR) with its raised concentrations (0.15 IU/ml, 0.30 IU/ml and 0.60 IU/ml) and prolonged treatment (3 h, 6 h, 12 h, 24 h). The concentrations with 0.60 IU/ml FSH could obviously promoted the expression of VEGF, bFGF and FSHR, but under this concentration FSH could also overstimulated the ovarian tissue leading to follicular loss. With the increase of culture time, the gene and protein expression of VEGF and bFGF both were up-regulated in all of the FSH added groups, but FSHR expression decreased when culture time exceeded 12 h. So we chose 0.30 IU/ml FSH added concentration and 6 h culture time as the FSH usage condition in functional revascularization verification experiment, and found that under this condition FSH promoted 2.5 times increase of vascular density in treated group than in control group after ovarian tissues transplantation. CONCLUSION: Ovarian intervention with 0.30 IU/ml FSH for 6 h is an optimal FSH usage condition which could accelerate the revascularization in the allotransplanted ovarian tissue and can not produce ovarian overstimulation.

Effects of aloperine on acute and inflammatory pain models in mice.

Graphical Abstract.

Protective effects of aloperine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion.

Aloperine (ALO), one of the alkaloids isolated from Sophora alopecuroides L., is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of ALO on neonatal rat primary-cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Treatment with ALO (25, 50, and 100 mg/l) attenuated neuronal damage (p < 0.01), with evidence of increased cell viability (p < 0.01) and decreased cell morphologic impairment. Furthermore, ALO increased mitochondrial membrane potential (p < 0.01), but inhibited intracellular-free calcium [Ca(2+)] i (p  < 0.01) elevation in a dose-dependent manner at OGD/RP. ALO also reduced the intracellular reactive oxygen species and malondialdehyde production and enhanced the antioxidant enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase and the total antioxidant capacity. The results suggested that ALO has significant neuroprotective effects that can be attributed to anti-oxidative stress.

[Clinical analysis of 95 patients with large vestibular aqueduct syndrome].

OBJECTIVE: To investigate the occurrence, genetic inheritance, and hearing loss conditions of large vestibular aqueduct syndrome (LVAS), and to measure the width of external aperture of vestibular aqueduct (VA) of LVAS, and to analyze the relationship between the hearing loss and the width of external aperture. METHODS: A retrospective review was conducted by the history, auditory, and vestibular function examinations in 95 patients (190 ears) of LVAS. The width of VA was measured by CT scanning criterion of each LVAS patients in the past 10 years (from 1992 to 2002). RESULTS: In 95 patients, there were male 65 cases and female 30 cases. The male cases was more than the females by a ratio of 2.2:1. Twelve cases (12.6%) would have familial genetic history. The average of the consult age was 7.6 years (range from 1.2 to 39 years). The most patients were misdiagnosed, the hearing deterioration originated from mild head trauma in 21 cases (22.1%), the hearing loss after common cold in 13 cases (13.6%). Nine cases (9.5%) misdiagnosed as sudden hearing loss, 5 cases (5.3%) as ototoxic hearing loss of Aminoglycoside antibiotic. The profound hearing loss was found in 172 ears (92.4%). The average width of external aperture of LVAS was 7.5 mm +/- 1.2 mm (mean +/- s, 77 cases, 154 ears). The level of hearing loss did not proportional to the width of VA. The hearing impairment could be derived from protein-rich endolymph refluxed into the cochlear and vestibule. CONCLUSION: The LVAS is distinct clinical entity characterized by fluctuate and progressive SNHL. The diagnosis depends upon the CT scan and MR image. If the hearing fluctuated and subsequently improved, the children were kept under conservation treatment. If the significantly decreased of hearing effected school performance, the cochlear implant might be considered.

[Design and preliminary use of the device of subjective visual vertical].

OBJECTIVE: The device of subjective visual vertical (SVV) was made to test the gravity orientation of subjects visual. METHODS: The normative value was established firstly in the right, left and both eyes respectively. Then the test was applied to evaluate the function of otolith function (utricular function) in normal adult subjects and examined the SVV in some patients suffered from acute unilateral vestibulopathy. RESULTS: The difference of the SVV among right, left and both eyes was not significant and the normative value was lower than +/- 2 degrees. No matter one eye or both eyes, SVV had the tendency to lateraliseze to the right. CONCLUSIONS: The SVV is a reliable choice to test the otolith vestibulopathy, which is at least suitable for acute phase. The bilateral eyes open mode is recommended to test the subjects suspected of utricuar dysfunction.