Fundamental & clinical pharmacology
-
Fundam Clin Pharmacol · Aug 2015
Randomized Controlled TrialThe genetic influences on oxycodone response characteristics in human experimental pain.
Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. ⋯ Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.
-
Fundam Clin Pharmacol · Feb 2015
Advanced glycation end products-induced chondrocyte apoptosis through mitochondrial dysfunction in cultured rabbit chondrocyte.
Advanced glycation end products (AGEs) are an important mediator in osteoarthritis (OA) and cause apoptosis in articular chondrocytes. Mitochondrial function is involved in modulating apoptosis of articular chondrocytes. This study was performed to investigate the mechanism of AGEs-induced chondrocyte apoptosis. ⋯ We found that AGEs induced apoptosis in primary rabbit chondrocytes, upregulation of ROS production, cytochrome c, and caspase-3 levels. Simultaneously, AGEs decreases the levels of ▵Ψm and ATP production; however, the antibody of AGEs (sRAGE) and antioxidant-N-acetylcys-teine (NAC) significantly reversed AGEs-induced the above damage thus to protect the cells from apoptosis. These observations suggested that the mechanism of AGEs-induced chondrocyte apoptosis was primarily via ROS production and mitochondria-mediated caspase-3 activation.
-
Fundam Clin Pharmacol · Feb 2015
The determination of histopathological and biochemical effects of the rabbit knee joint injected dexketoprofen trometamol.
This study was conducted to investigate possible histopathological effects and biochemical reflections of intra-articular dexketoprofen trometamol. A total of 24 New Zealand rabbits were included in the study. Blood sampling was carried out from all animals on the first day, then they were randomly allocated either to the control group (Group C, n = 9) or the dexketoprofen trometamol group (Group D, n = 15). ⋯ Basal TNF-α levels were higher compared with day 1 in Group C1, and IL-6 and CRP levels were higher in Group D3. Also, none of the increases in these values are supported by histopathological evaluation results. Consequently, we suppose that dexketoprofen trometamol does not cause histopathological deterioration in articular cartilage of rabbits, and the increases in biochemical parameters exclusively are not clinically significant.
-
Fundam Clin Pharmacol · Dec 2014
Comparative StudyLow doses of dextromethorphan have a beneficial effect in the treatment of neuropathic pain.
N-methyl-D-aspartate receptor (NMDAR) antagonists may be given in persistent neuropathic pain, but adverse events especially with ketamine may limit their clinical use. Less central and cognitive adverse events are described with dextromethorphan and memantine. These molecules have been explored in many preclinical and clinical studies, but data are conflicting as regards neuropathic pain alleviation. ⋯ Dextromethorphan, but not memantine, reversed neuropathic pain (NP) symptoms, restored spatial memory integrity and decreased the expression of pTyr(1336)NR2B. Following postoperative administration of dextromethorphan, this study has demonstrated for the first time a concordance between behaviour, cognitive function and molecular events via pTyr(1336)NR2B for neuropathic pain alleviation. Confirmation of these findings in patients would constitute a major step forward in the treatment of neuropathic pain and in the improvement of cognitive function and quality of life.
-
Fundam Clin Pharmacol · Dec 2014
Investigation of effects of levobupivacaine injection to rabbit knee joint on histopathologic changes of joint cartilage tissue and changes of serum biochemical parameters.
The aim of this study is to evaluate the effects of intra-articular levobupivacaine on rabbit knee articular cartilage and certain biochemical parameters in the blood. A total of 24 New Zealand rabbits were included to study. Blood sampling was carried out in all animals on the first day, then the subjects were randomly allocated either to the control group (Group C, n = 9) or to the levobupivacaine group (Group L, n = 15). ⋯ It is concluded that levobupivacaine does not lead to significant histologic changes in rabbit articular cartilage. Significant elevations of biochemical parameters being generally found in the C Group, it is thought that such elevations are not linked to levobupivacaine. Intra-articular levobupivacaine may be a safe alternative for use in post-operative analgesia.