Chondroitin sulfate attenuates formalin-induced persistent tactile allodynia

AbstractWe examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord

Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice

ABSTRACT Renin-angiotensin system (RAS) activity increases under hyperglycemic states, and is thought to be involved in diabetic complications. We previously demonstrated that angiotensin (Ang) II, a main bioactive component of the RAS, might act as a neurotransmitter and/or neuromodulator in the transmission of nociceptive information in the spinal cord. Here, we examined whether the spinal Ang II system is responsible for diabetic neuropathic pain induced by streptozotocin (STZ). Tactile allodynia was observed concurrently with an increase in blood glucose levels the day after mice received STZ (200 mg/kg, i.v.) injections. Tactile allodynia on day 14 was dose-dependently inhibited by intrathecal administration of losartan, an Ang II type 1 (AT1) receptor antagonist, but not by PD123319, an AT2 receptor antagonist. In the lumbar dorsal spinal cord, the expression of Ang II, Ang converting enzyme (ACE), and phosphop38 mitogen-activated protein kinase (MAPK) were all significantly increased on day 14 after STZ injection compared with vehicletreated controls, whereas no differences were observed among AT1 receptors or angiotensinogen levels. Moreover, the increase in phospho-p38 MAPK was significantly inhibited by intrathecal administration of losartan. These results indicate that the expression of spinal ACE increased in STZ-induced diabetic mice, which in turn led to an increase in Ang II levels and tactile allodynia. This increase in spinal Ang II was accompanied by the phosphorylation of p38 MAPK, which was shown to be mediated by AT1 receptors

断続的なREM断眠ストレス負荷誘発性マウス腸管輸送能の亢進

Clinical reports have shown that irritable bowel syndrome (IBS) is comorbid with anxiety and stress-related events. The treatment of rapid eye movement (REM) sleep deprivation (REMSD) is a potent stressor in animals. Stress in humans commonly results in gastrointestinal dysfunction, which is characterized by its symptomatology because the etiology is completely unknown. In the present study, we found that intermittent REMSD treatment (20 h/day) for 3 days markedly increased gastrointestinal transit of charcoal meal in mice. The accelerated gastrointestinal transit was significantly inhibited by both diazepam (1 and 2 mg/kg, p.o.) and by a peripheral , μ-opioid receptor agonist loperamide (3 and 10 mg/kg, p.o.), which are clinically used to treat diarrhea-predominant IBS. The ID_ values of loperamide in cage-control (CC) mice and intermittent REM sleep deprived mice were 18.14mg/kg and 6.78mg/kg, respectively. These results indicate that intermittent REMSD treatment increases gastrointestinal transit; this model may be useful for evaluating the effects of drugs on diarrhea-predominant IBS, and the supersensitivity of peripheral , μ-opioid receptor may be involved in the accelerated gastrointestinal transit

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Involvement of spinal angiotensin II system in streptozotocin-induced diabetic neuropathic pain in mice MOL #104133 2 Running Title: Streptozotocin-induced neuropathic pain and angiotensin II

Abstract: 234/250 Introduction: 535/75