ABSTRACT
Background: Ghrelin is a peptide with attenuating effect on inflammatory pain. Both anti- and pro-inflammatory mediators have a role in the nociception and development of pain and hyperalgesia. IL-10 and TGF-beta are anti-inflammatory cytokines and inhibit the expression of pro-inflammatory cytokines related to peripheral and central inflammatory pain. In this study, the effects of i.p. injection of ghrelin on the early and the late phases of pain, as well as serum levels of IL-10 and TGF-beta, as anti-inflammatory cytokines, were investigated in formalin-induced pain in male rats
Methods: Adult male Wistar rats [n=48] were randomly divided into six groups: control, formalin+saline, ghrelin [40, 80, and 160 microg/kg], and morphine. Ghrelin was administered i.p. 30 min before inducing pain by formalin. Pain induced by intraplantar [i.pl.] injection of 50 microl formalin 5%, and pain behavior was studied for 60 min. Serum IL-10 and TGF-beta levels were assessed by ELISA method
Results: The findings of the present study showed that ghrelin with high doses [80 and 160 microg/kg] significantly reduced pain intensity in both the early and the late phases of pain. The serum levels of cytokines, IL-10, and TGF-beta1 showed a significant elevation with ghrelin at dose of 160 microg/kg
Conclusion: Ghrelin is effective in reducing the intensity of both the early and the late phases of inflammatory pain. It seems that ghrelin exerts its analgesic effects in part by increasing the serum levels of anti-inflammatory cytokines
ABSTRACT
Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke neurodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats. The study was carried out on 60 adult male wistar rats, weighing 200- 250 gr. The rats were randomly divided into three groups: control, stress and stress + dalteparin [SD] groups. Animals in the stress and stress + dalteparin group were exposed to chronic stress for 4 weeks. Animals in the stress + dalteparin [SD] group received dalteparin [70,100 and 140 IU/kg/days i.p.] during the stress period. After the last stressor animals were sacrificed and concentration of IL-6 in serum was measured using ELISA. All animals were reperfused and their brains were processed for histological analysis through Nissl analysis. We found that the serum concentration of IL-6 was significantly higher in the CMS [Chronic Mild Stress] exposure group than in the control group [p<0.05]. Moreover, dalteparin, dose dependently decreased IL-6 concentration in the SD groups. Chronic stress also resulted in significant cell loss in hippocampal CA1, CA3 and hilus. Dalteparin markedly inhibited the decreases in number of hippocamoal CA1 and CA3 [p<0.01] and hilus [p<0.05] neurons caused by chronic stress. Chronic stress damages hippocampal CA1, CA3 and hilus neurons, and dalteparin protects hippocampus from damage induced by chronic stress