Gabapentin Activates Spinal Noradrenergic Activity in Rats and Humans and Reduces Hypersensitivity after Surgery

Background: Gabapentin has been reported to inhibit various acute and chronic pain conditions in animals and humans. Although the efficacy of gabapentin depends on the [alpha]2[delta] subunit of voltage-gated calcium channels, its analgesic mechanisms in vivo are still unknown. Here, the authors tested the role of spinal noradrenergic inhibition in gabapentin's analgesia for postoperative pain.

Methods: Gabapentin was administered orally and intracerebroventricularly to rats on the day after paw incision, and withdrawal threshold to paw pressure was measured. The authors also measured cerebrospinal fluid concentration of norepinephrine and postoperative morphine use after surgery in patients who received oral placebo or gabapentin.

Results: Both oral and intracerebroventricular gabapentin attenuated postoperative hypersensitivity in rats in a dose-dependent manner. This effect of gabapentin was blocked by intrathecal administration of the [alpha]2-adrenergic receptor antagonist idazoxan and the G protein-coupled inwardly rectifying potassium channel antagonist tertiapin-Q, but not by atropine. In humans, preoperative gabapentin, 1,200 mg, significantly increased norepinephrine concentration in cerebrospinal fluid and decreased morphine requirements.     

The UK Diabetes Research Network--an opportunity and a challenge.

The Department of Health has funded a national diabetes network to support clinical research. The network will facilitate recruitment into clinical trials and has been widely welcomed by clinicians. However, if the network is to reach its full potential, all those involved will need to advocate a change in attitude towards clinical trials and research, encouraging participation and contribution of data. Clinicians need to be willing to take a proactive view about research studies, and to encourage patients to adopt a positive and altruistic attitude towards trial participation. The future of trials and other important clinical research in the UK may depend on it.     

Trans fat intake lowers total cholesterol and high-density lipoprotein cholesterol levels without changing insulin sensitivity index in Wistar rats

Epidemiologic studies have demonstrated that trans fat intake increases the risk of some chronic diseases. We hypothesize that trans fat intake would increase the risk of cardiovascular disease and type 2 diabetes mellitus by changing the lipid profile in plasma, the secretion of adipokines in adipose tissue, and the insulin sensitivity. Accordingly, the major objective of present study was to investigate the effect of dietary intake of trans fat on lipid profile, insulin sensitivity, and adipokine levels in plasma. Two groups of Wistar rats were fed a diet containing 4.5% trans fat or a control diet containing no trans fat for 16 weeks. Fasting glucose level was monitored every 2 weeks. At the end of feeding experiment, blood, heart, kidney, liver, omental adipose tissue, and semitendinosus muscle were collected. The trans fat content in organs, lipid profile, adipokine, insulin, and glucose levels in plasma were analyzed. The trans fat content in adipose tissue, heart, kidney, liver, and muscle of rats fed trans fat were 169.9, 0.6, 1.2, 1.7, and 2.5 mg/g samples, respectively. The trans fat content in these organs contributed to 15.9%, 1.2%, 2.3%, 4.3%, and 6.1% of the total fat, respectively. The plasma glucose level, insulin level, and insulin sensitivity index were not significantly different between the trans fat and control groups. The results indicated that trans fat intake might not be related to insulin resistance. However, lipid profile and plasma adipokine levels were significantly changed after trans fat feeding. The trans fat fed group showed significantly lower total cholesterol and high-density lipoprotein cholesterol levels than the control group. The decreased high-density lipoprotein cholesterol level may indicate the detrimental effect of trans fat intake on lipid profile. Adiponectin and resistin levels were significantly higher in the trans fat group than the control group. Leptin levels were significantly lower in the trans fat group than the control group. The results indicated that dietary intake of trans fat can significantly change the adipokine levels, but the possible links between adipokine level change caused by trans fat intake and metabolic effects of this change need further investigations.