The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice.Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS.CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice.Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS.CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

[Effects of aerobic exercise and glutamine on oxidative stress and expression of related factors in type 2 diabetic rats].

OBJECTIVE: To investigate the effects of aerobic exercise and glutamine (Gln) on anti-oxidative stress and inflammatory factors in type 2 diabetes mellitus (T2MD) rats. METHODS: Diabetic rat model was induced by streptozotocin (STZ). Fifty 6-week old male SD rats were randomly divided into 5 groups (n=10), including quiet control group (N), diabetes control group (D), diabetic aerobic exercise group (DE), diabetic glutamine group (DG) and diabetic aerobic exercise glutamine group (DEG). After 6 weeks, the related indicators of glucose and lipid metabolism, anti-oxidative stress and inflammatory factors in diabetic rats were detected, and the possible mechanism affecting inflammatory response were explored. RESULTS: Compared with group N, the levels of serum malondialdehyde(MDA), blood glucose, total cholesterol(TC), triglyceride(TG), insulin, leptin and tumor necrosis factor-α(TNF-α) in group D were increased significantly (P＜0.01). Compared with group D, serum levels of MDA, blood glucose, TC, TG, insulin, leptin and TNF-α in three intervention groups were decreased significantly, while the levels of SOD, GSH-Px and adiponectin were increased, and the combined effect was more obvious (P＜0.01). CONCLUSION: Both aerobic exercise and Gln can relieve the glucose and lipid metabolism and disturbance, oxidative stress injury and inflammation in diabetic rats.

The Molecular Signatures of Acute-immobilization-induced Antinociception and Chronic-immobilization-induced Antinociceptive Tolerance

In the present study, the productions of antinociception induced by acute and chronic immobilization stress were compared in several animal pain models. In the acute immobilization stress model (up to 1 hr immobilization), the antinociception was produced in writhing, tail-flick, and formalin-induced pain models. In chronic immobilization stress experiment, the mouse was enforced into immobilization for 1 hr/day for 3, 7, or 14 days, then analgesic tests were performed. The antinociceptive effect was gradually reduced after 3, 7 and 14 days of immobilization stress. To delineate the molecular mechanism involved in the antinociceptive tolerance development in the chronic stress model, the expressions of some signal molecules in dorsal root ganglia (DRG), spinal cord, hippocampus, and the hypothalamus were observed in acute and chronic immobilization models. The COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus were elevated in acute immobilization stress, but were reduced gradually after 3, 7 and 14 days of immobilization stress. Our results suggest that the chronic immobilization stress causes development of tolerance to the antinociception induced by acute immobilization stress. In addition, the COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus may play important roles in the regulation of antinociception induced by acute immobilization stress and the tolerance development induced by chronic immobilization stress.

[Effects of aerobic exercise combined with melatonin on osteoporosis of type II diabetic rats].

OBJECTIVE: To investigate the effects of aerobic exercise and melatonin on osteoporosis in type 2 diabetic rats. METHODS: Sixty fe male SD rats were randomly divided into the control group (n=10) and the diabetic model group (n=50). The rats in the control group(N group) did not receive any intervention, and the rats in the type Ⅱ diabetic group (D) was injected with streptozocin(STZ) at the dose of 35 mg/kg by intraperitoneally. One week later, rats with blood glucose greater than 16.7 mmol/L were successfully modeled for type Ⅱ diabetes. Forty diabetic rats were randomly divided into diabetic control group (D), diabetes + aerobic exercise group(CDE),diabetes + melatonin group (DM), diabetes mellitus + aerobic exercise + melatonin group (DEM), 10 rats in each group. The rats in DE and DEM groups were treated with 20 min aerobic exercise for 6 weeks. The rats in DM group and DEM group were given 40 mg/kg of melatonin per day. The body weight, vertebrae and left and right femur bone mineral density (BMD) of the rats in each group were observed. Malondialdehyde(MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), serum total calcium (Ca), inorganic phosphate (P) and parathyroid hormone (PTH) were detected. RESULTS: Compared with N group, body weight, serum SOD, GSH-Px levels, blood Ca, lumbar and femoral BMD of rats in group D were decreased significantly (P < 0.05 or P < 0.01). The levels of blood glucose, serum MDA and serum PTH were increased sig-nificantly (P < 0.01), the level of blood P had no changes (P > 0.05); compared with group D, DE group, DM group rats body weight, serum SOD, GSH-Px levels, blood Ca, lumbar spine and femur about BMD were increased significantly (P < 0.05 or P < 0.01). The levels of blood glucose, serum MDA and serum PTH were decreased significantly (P < 0.05 or P < 0.01), the level of blood P had no changes (P > 0.05). The effects in diabetic rats treated with aerobic exercise and melatonin at the same time were much better. CONCLUSIONS: Both aero-bic exercise and melatonin can improve diabetic osteoporosis, and the effect of both joint intervention is more significant, it may be associated with oxidative stress by increasing the ability of diabetic rats, regulate glucose metabolism in order to effectively reduce the calcium and PTH, improve BMD to alleviate osteoporosis.

[The experimental study on melatonin gastro intestinal motility and plasma levels of stress hormones in overtraining rat].

OBJECTIVE: To study the effect of melatonin on the gastrointestinal motility and plasma levels of the stress hormone in overtraining rats. METHOD: Thirty adult SD rats were randomly divided into three groups (n = 10): control group, over-training group, melatonin intervention group. 30 min before each training, rats in the control and over-training groups were fed with normal saline (15 mg/kg) once a day and 5 times per week, while rats in the melatonin intervention group were administrated with melatonin, perfusion in the intervention group (15 mg/kg). Excessive training group and melatonin intervention group rats were subjected to excessive training at 5 times a week for 6 weeks. After 6 weeks, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma motilin (MTL) and calcitonin gene-related peptide (CGRP), cortisol (CORT) and catecholamines (CA) were observed in all groups. RESULTS: Compared with the control group, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma MTL, CORT and CA were increased significantly (P < 0.01) while the content of CGRP was reduced (P < 0.01) in over-training group. After treated with melatonin, this trend was reversed, that was, the gastric emptying rate, small intestinal propulsion ratio and levels of plasma MTL, CORT and CA were surpressed significantly (P < 0.01) while the content of CGRP was improved obviously (P < 0.01) in over-training group. CONCLUSION: Melatonin plays an important role in protecting gastrointestinal tract from dysfunction, in which MTL, CGRP, CORT and CA are all involved.