Human Experimental Pain Models: A Review of Standardized Methods in Drug Development.

Human experimental pain models: A review of standardized methods in drug development.

J Res Med Sci. 2012 Jun; 17(6): 587-95
Reddy KS, Naidu MU, Rani PU, Rao TR

Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical) can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding. HubMed – drug


Toxicity effects of methamphetamine on embryonic stem cell-derived neuron.

J Res Med Sci. 2012 May; 17(5): 470-4
Meamar R, Dehghani L, Karamali F

Methamphetamine (MA) is the most popular recreational drug. According to potential neurotoxicity of this agent, it can cause deleterious effects on neural differentiation of embryo, if MA is used during the child bearing period. In recent decades, undifferentiated pluripotent embryo-derived stem cell lines, resembling early embryonic stages, have been used to analyze the toxic effects of components in vitro. Thus, this study aims at assessing toxic effects of MA on embryonic stem cell (ESC)-derived neuronal cells during differentiation in a pharmacological model. MATERIALS ANS METHODS: ESC line Royan was used throughout this study. The effect of MA on neural differentiation was assessed during two periods, group 1: MA (10, 100, 200,500, 750, 1000 ?M concentrations) was added during EB formation, group 2: MA (10, 50, 70, 100, 200, 500 ?M concentrations) was added after the generation of neural precursors. Then cells were evaluated for neuronal markers by immunocytochemistry and RT-PCR. One way ANOVA followed by the post hoc test was used to analyze data.The declining in outgrowth of dendrites was observed in neural morphology in a dose dependent manner. The ID50 (Inhibition of neuronal differentiation) of groups 1 and 2 were 130 and 400 ?M, respectively. By using RT-PCR, in comparison with MAP2, no significant change was observed in Nestin expression.Our data on neuronal toxicity were consistent with in vivo and in vitro studies. We concluded that ESCs can be used as an efficient model to assess the toxicity of drugs. HubMed – drug


The effect of Aloe vera leaf gel on fatty streak formation in hypercholesterolemic rabbits.

J Res Med Sci. 2012 May; 17(5): 439-42
Dana N, Javanmard SH, Asgary S, Asnaashari H, Abdian N

Atherosclerosis is a complex disease that is associated with a variety of etiologic factors such as hyperlipidemia and inflammation. Aloe vera (Liliaceae family) has been used traditionally as an anti-inflammatory drug. The aims of this survey were to define the beneficial effects of Aloe vera leaf gel on some of the atherosclerosis risk factors, and also fatty streak formation in hypercholesterolemic rabbits. MATERIALS ANS METHODS: 32 white male rabbits were randomly divided into four experimental groups (n = 8, each). During the study, the animals had a standard diet (control group), high cholesterol diet (HC group), high cholesterol diet with Aloe vera leaf gel (3.2%v/v) (HC+ Aloe group) and Aloe vera leaf gel (Aloe group) for 30 days. Fasting blood samples were collected from all animals at the beginning and end of the study. Then total cholesterol (TC), fasting blood sugar (FBS), triglyceride (TG) and CRP were measured before and after experimental periods. By the end of the study, the aortas were removed and investigated for atherosclerosis plaque formation.Significant differences were observed in TC and CRP levels of the high-cholesterol diet with Aloe vera and the high-cholesterol diet alone (p < 0.05). The formation of fatty streaks in the aorta was also significantly lower in the same animals under the influence of dietary Aloe vera(p < 0.05). The control and Aloe group did not show any evidence of atherosclerosis. No significant difference was found between the groups in TG and FBS.The data suggests that Aloe vera has beneficial effects on the prevention of fatty streak development; it may reduce the development of atherosclerosis through modification of risk factors. However, further studies are needed to understand the mechanisms whereby this plant exerts its anti-atherosclerotic effects. HubMed – drug