Pressure hyperalgesia in hind limb suspended rats.

INTRODUCTION: Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. METHODS: Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. RESULTS: Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). DISCUSSION: The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.

Brief communication: Effects of soy-protein diet on elevated brain lipid peroxide levels induced by simulated weightlessness.

The influence of soy-protein diet on brain lipid peroxidation in female rats was studied using a tail-suspension model of weightlessness. The study tested the efficacy of diets containing 0% or 11.1% soy-protein in 4 groups of female Sprague Dawley rats that were maintained with or without tail-suspension for a period of 3 weeks. At term, the whole brain was removed, segmented, and analyzed for malondialdehyde (MDA) as an index of lipid peroxidation. Brain levels of MDA were significantly higher in both tail-suspended groups than in the non-suspended control groups on the same diet, (p<0.05). The high soy-protein diet decreased MDA levels significantly, compared to the 0% soy-protein groups (p<0.05). Furthermore, MDA levels were significantly lower in the tail-suspended group on high soy-protein diet, compared to the corresponding 0% soy-protein group. In conjunction with previous findings in male rats, these data indicate that tail-suspension increases brain MDA levels in rats regardless of gender, and that a diet rich in soy-protein decreases the brain MDA level in both the non-suspended and tail-suspended groups. These observations imply that the soy-protein diet has a protective antioxidant effect during both the basal condition and the stressful condition.

Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension.

The aim of this study was to compare physiological effects of hindlimb suspension (HLS) in tail- and pelvic-HLS rat models to determine if severe stretch in the tail-HLS rats lumbosacral skeleton may contribute to the changes traditionally attributed to simulated microgravity and musculoskeletal disuse in the tail-HLS model. Adult male Sprague-Dawley rats divided into suspended and control-nonsuspended groups were subjected to two separate methods of suspension and maintained with regular food and water for 2 weeks. Body weights, food and water consumption, soleus muscle weight, tibial bone mineral density, random plasma insulin, and hindlimb pain on pressure threshold (PPT) were measured. X-ray analysis demonstrated severe lordosis in tail- but not pelvic-HLS animals. However, growth retardation, food consumption, and soleus muscle weight and tibial bone density (decreased relative to control) did not differ between two HLS models. Furthermore, HLS rats developed similar levels of insulinopenia and mechanical hyperalgesia (decreased PPT) in both tail- and pelvic-HLS groups. In the rat-to-rat comparisons, the growth retardation and the decreased PPT observed in HLS-rats was most associated with insulinopenia. In conclusion, these data suggest that HLS results in mild prediabetic state with some signs of pressure hyperalgesia, but lumbosacral skeleton stretch plays little role, if any, in these pathological changes.

Effects of aminoguanidine on tissue oxidative stress induced by hindlimb unloading in rats.

We investigated the effects of hindlimb unloading (HLU) on malondialdehyde (MDA), a biomarker for oxidative stress, and glutathione (GSH) levels in tissues of rats. Aminoguanidine (AG), a nucleophilic hydralazine compound and an in vivo antioxidant against reactive oxygen species (ROS) and lipid peroxidation, was used to confirm the HLU-induced oxidative response. Three groups of rats were used: Group 1 was a loaded control group that was maintained on drinking water only; Groups 2 and 3 were hindlimb unloaded (HLU) groups that were maintained on drinking water and on AG in drinking water, respectively. The hindlimb unloaded rats maintained on tap water had significantly elevated MDA levels in 7 tissues (brain, lung, pancreas, kidney, intestine, heart, liver) when compared to the paired hindlimb loaded controls (p <0.05). In contrast, the hindlimb unloaded rats maintained on AG in drinking water had no increase in tissue MDA levels when compared to the loaded controls; moreover, their tissue MDA levels were significantly reduced from the HLU group on tap water (p <0.05). In HLU rats maintained on AG, there were no changes in tissue GSH levels with the exception of brain, where GSH levels were significantly reduced when compared to the other groups (p <0.05). In summary, HLU induced an oxidative response in rats and this response was reduced significantly by ingestion of AG. These results suggest the potential application of AG in the diet of astronauts living in a stressful environment.