Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the roles of the calmodulin-stimulated adenylyl cyclases (AC1 and AC8) in morphine-induced analgesia, tolerance, physical dependence, and conditioned place preference, we used mice having targeted disruptions of either the AC1 or AC8 genes or both genes [double knockout mice (DKO)]. Mice lacking either AC1 or AC8 genes or DKO did not differ from wild-type mice in short-term antinociceptive responses to morphine measured in the tail-flick analgesia assay. Morphine tolerance that developed immediately within 3 h of morphine administration (10 mg/kg s.c.) was significantly attenuated in DKO mice and AC8 single knockout mice. Tolerance induced continually by daily injections of morphine (10 mg/kg s.c.) was also reduced in DKO mice. In DKO mice continually treated with morphine, there was a significant reduction in withdrawal behaviors, including reduced wet-dog shakes and forepaw tremor after naloxone injection (10 mg/kg i.p.). Morphine produced hyperlocomotion and conditioned place preference in wild-type mice, whereas DKO mice displayed significantly less hyperlocomotion and conditioned place preference. Furthermore, the significant increase in phosphorylated cAMP-response element binding protein (CREB) staining in ventral tegmental area induced by long-term morphine treatment was not evident in DKO mice, suggesting that CREB activation by morphine requires cAMP generated by AC1 and AC8. These results support the hypothesis that calmodulin-stimulated adenylyl cyclases are important mediators of the neuronal responses to morphine.
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PMID:Calmodulin-stimulated adenylyl cyclase gene deletion affects morphine responses. 1691 43

In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, PC12 cells were co-cultured with xylazine, and extracellular regulated protein kinase (ERK) siRNA and protein kinase A (PKA) siRNA were transfected into cells to identify changes of relevant indicators. Our data showed that xylazine influenced the level of adenosine triphosphate (ATP) ase and cyclic adenosine monophosphate (cAMP), and regulated the expression of GluR1, ERK, PKA, cAMP-response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) in the nervous system. However, xylazine did not significantly affect the expression of GluR2 and protein kinase C (PKC). Together, these results indicated that xylazine might exert sedation and analgesia by regulating the PKA/ERK/CREB signaling pathway.
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PMID:Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell. 3095 55