Characterization of changes of pain behavior and signal transduction system in food-deprived mice.

Fasting in general causes several metabolic changes. In the present study, we examined the possible changes of several types of nociception during the food deprivation were investigated in mice. After the mice were forced into the fasting for 12, 24, or 48 h, the changes of nociception were measured by the tail-flick, writhing, formalin or von-frey tests. We found that the nociceptive behavior induced by intraperitoneally (i.p.) administered acetic acid (writhing response) or intraplantar injection of 5% formalin into the hind-paw were reduced in fasted group. In addition, the tail-flick response and threshold for nociception in mechanical von-frey test were also elevated in fasted group. Moreover, the p-CREB and p-ERK levels in the dorsal root ganglia (DRG) and the spinal cord were reduced in food-deprived group. Furthermore, p-AMPKα1 expressions in DRG and the spinal cord were up-regulated, whereas p-mTOR in DRG and the spinal cord was down-regulated in food-deprived group. Our results suggest that the chemical, mechanical, and thermal nociceptions appear to be reduced in a food-deprived mouse group. Additionally, reduction of nociception in food-deprived group appears to be closely associated with the expressions of several signal transduction molecules such as ERK, CREB, AMPKα1 and mTOR proteins in DRG and the spinal cord.

Anti-Nociceptive Effect and Standardization from Mixture of Agrimonia pilosa Ledeb and Salvia miltiorrhiza Bunge Extracts.

Agrimonia pilosa Ledeb has been previously reported to produce an anti-nociceptive effect in ICR mice in both tail-flick and hot-plate tests. Studies have shown that Salvia miltiorrhiza Bunge, also renowned in traditional Chinese medicine, is an effective anti-inflammatory treatment. Among the extraction solvents investigated, a 50% ethanol (EtOH) extract of A. pilosa produced the highest anti-nociceptive effect in monosodium uric acid-induced gout pain models and the greatest yield. The 80% EtOH extract of S. miltiorrhiza moderately inhibited lipopolysaccharide-induced nitric oxide release from RAW 264.7 murine macrophages and exhibited outstanding yield. The mixture of optimized A. pilosa and S. miltiorrhiza extracts were evaluated for enhanced anti-nociceptive effects in gout arthritis treatment. To control extract quality, four marker compounds were determined using an HPLC-DAD method. A 1:1 mixture of A. pilosa 50 and S. miltiorrhiza 80% EtOH extracts of produced better results than when the extracts were administered individually.

Antinociceptive profiles and mechanisms of centrally administered oxyntomodulin in various mouse pain models.

In the present study, the antinociceptive profiles of oxyntomodulin were examined in ICR mice. Oxyntomodulin administered intrathecally (i.t.) and intracerebroventricularly (i.c.v.) (from 1 to 5µg/5µl) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Moreover, cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced by i.t. or i.c.v. treatment with oxyntomodulin during the second, but not the first phase. In addition, the cumulative nociceptive response time after i.t. injection with substance P (0.7µg), glutamate (20µg), and pro-inflammatory cytokines such as TNF-α, IL-ß or IFN-γ (100pg/5µl) was diminished by spinally or supraspinally administered oxyntomodulin. However, i.t. and i.c.v. treatment with oxyntomodulin did not affect latencies of the tail-flick and hot-plate paw-licking responses. Furthermore, the i.t. pretreatment with yohimbine (adrenergic receptor antagonist), but not naloxone (an opioid receptor antagonist) or methysergide (a serotonergic receptor antagonist), attenuated antinociceptive effect induced by oxyntomodulin administered i.c.v. in the writhing test. The i.c.v. or i.t. pretreatment with oxyntomodulin attenuated formalin-induced increase of phosphorlated ERK (p-ERK) expression in the spinal cord. Our results suggest that centrally administered oxyntomodulin shows an antinociceptive property in various pain models except for thermal-induced nociception. Furthermore, supraspinally administered oxyntomodulin-induced antinociception may be mediated by spinal adrenergic receptors, but not serotonergic and opioidergic receptors. Furthermore, the antinociception induced by oxyntomodulin appears to be mediated by reduced formalin-induced p-ERK expression in the spinal cord.

Family history of chronic renal failure is associated with malnutrition in Korean hemodialysis patients.

The present study was to investigate the nutritional status and factors related to malnutrition in end-stage renal disease (ESRD) patients requiring hemodialysis (HD) in South Korea. Subjects were ESRD outpatients from general hospitals or HD centers in Seoul referred to the dialysis clinic for maintenance HD care. A total of 110 patients (46 men and 64 women; mean ages 58.6 +/- 1.0 y) were eligible for this study. The family history of chronic renal failure (CRF) was considered positive if a patient reported having either a first-degree or second-degree relative with CRF. Malnutrition was defined as a triceps skinfold thickness or mid-arm muscle circumference below the fifth percentile for age and sex and forty-seven of the 110 patients were malnourished. Almost all (94%) patients had anemia (hemoglobin: <13 g/dL for men and <12 g/dL for women). Energy intake was below the recommended intake levels of energy [30-35 kcal/kg ideal body weight (IBW)] and protein (1.2 g/kg IBW) in 60% of patients. The duration of HD was longer in malnourished HD patients (P=0.0095). Malnutrition was more prevalent in women (P=0.0014), those who never smoked (P=0.0007), nondiabetic patients (P=0.0113), and patients with bone diseases (P=0.0427), adequate HD (spKt/V>/=1.2) (P=0.0178), and those with a family history of CRF (P=0.0255). Multiple logistic regression was used to examine the relationship between malnutrition and potential risk factors. After adjusting for age, sex, and other putative risk factors for malnutrition, the OR for malnutrition was greater in HD patients with a family history of CRF (OR, 3.290; 95% CI, 1.003-10.793). Active nutrition monitoring is needed to improve the nutritional status of HD patients. A family history of CRF may be an independent risk factor for malnutrition in Korean HD patients. A follow-up study is needed to investigate whether there is a causal relationship between a family history of CRF and malnutrition in Korean ESRD patients.

Nutritional status and the role of diabetes mellitus in hemodialysis patients.

This study was aimed to investigate the nutritional status and the role of diabetes mellitus in hemodialysis (HD) patients. Anthropometric, biochemical, and dietary assessments for HD 110 patients (46 males and 64 females) were conducted. Mean body mass index (BMI) was 22.1 kg/m(2) and prevalence of underweight (BMI<18.5 kg/m(2)) was 12%. The hypoalbuminemia (<3.5 g/dl) was found in 15.5% of the subject, and hypocholesterolemia (<150 mg/dl) in 46.4%. About half (50.9%) patients had anemia (hemoglobin: <11.0 g/dL). High prevalence of hyperphosphatemia (66.4%) and hyperkalemia (43.5%) was also observed. More than 60 percent of subjects were below the recommended intake levels of energy (30-35 kcal/kg IBW) and protein (1.2 g/kg IBW). The proportions of subjects taking less than estimated average requirements for calcium, vitamin B(1), vitamin B(2), vitamin C, and folate were more than 50%, whereas, about 20% of the subjects were above the recommended intake of phosphorus and potassium. Diabetes mellitus was the main cause of ESRD (45.5%). The diabetic ESRD patients showed higher BMI and less HD adequacy than nondiabetic patients. Diabetic patients also showed lower HDL-cholesterol levels. Diabetic ESRD patients had less energy from fat and a greater percentage of calories from carbohydrates. In conclusion, active nutrition monitoring is needed to improve the nutritional status of HD patients. A follow-up study is needed to document a causal relation between diabetes and its impact on morbidity and mortality in ESRD patients.