RESUMO
The aim of this research proposal was to investigate the effects of tetrahydropalmatine (THP) on gene expression in a post-traumatic stress disorder (PTSD) rodent model. Eighty male Sprague-Dawley rats were randomly assigned to the nonstressed groups or the 3-day restraint shock PTSD rodent model groups. There were four groups within the nonstressed rats (control, THP, midazolam, and midazolam with THP) and four groups within the stressed rats (control, THP, midazolam, and midazolam with THP). After injection the subjects were euthanized and the amygdala and hippocampus were sent for reverse transcriptase-polymerase chain reaction gene expression analysis. Of the genes interrogated, 17 genes in the amygdala and 18 genes in the hippocampus were found to have significant changes in gene expression and regulation. Significant transcriptional fold changes were found in important genes involved in dopamine, serotonin, acetylcholine, and gamma-aminobutyric acid neurotransmitter systems. The results provide quantifiable data demonstrating gene expression changes in PTSD-stressed and nonstressed rats receiving various treatments. These findings contribute important data to the limited molecular details pertaining to the neurobiology of PTSD.
Assuntos
Analgésicos não Narcóticos/farmacologia , Alcaloides de Berberina/farmacologia , Encéfalo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores de Neurotransmissores/metabolismo , Transtornos de Estresse Pós-Traumáticos/patologia , Adjuvantes Anestésicos/farmacologia , Adjuvantes Anestésicos/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Análise de Variância , Animais , Alcaloides de Berberina/uso terapêutico , Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Midazolam/farmacologia , Midazolam/uso terapêutico , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Receptores de Neurotransmissores/genética , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológicoRESUMO
The distribution and physiological role of the neuropeptide, arginine vasopressin (AVP), and its three receptor subtypes, V1a, V1b and V2, has been well described. A fourth AVP receptor, VACM-1, was recently discovered and appears to be a member of the cullin gene family. The objective of this research is to characterize VACM-1 receptor mRNA expression in the CNS as well as in various tissues and organs of the laboratory rat. Northern blotting of poly(A) + RNA from various tissues demonstrated the size of VACM-1 MRNA in the rat is approximately 6.3 kb. RT-PCR indicated the transcript is present in all twelve tissues examined: brainstem, cerebral cortex, cerebellum, hypothalamus, aorta, gastrointestinal tract, heart, kidney medulla, liver, lung, skeletal muscle, and spleen. Quantitative realtime PCR confirmed RT-PCR results that VACM-1 mRNA is in all organs and tissues and expression levels are similar in all tissues examined. The transcript encoding VACM-1, a novel AVP receptor, appears to be ubiquitously expressed in various tissues of the laboratory rat. VACM-1 shares some similarities with both V1 and V2 receptors, as it binds AVP analogues that independently recognized either of these receptors. Therefore, many functions ascribed to activation of the previously known AVP receptors could at least in part be mediated by VACM-1.
Assuntos
Sistema Nervoso Central/química , Proteínas Culina , Proteínas de Membrana/genética , RNA Mensageiro/análise , Receptores de Vasopressinas/genética , Animais , Aorta/química , Northern Blotting , Tronco Encefálico/química , Cerebelo/química , Córtex Cerebral/química , Sistema Digestório/química , Hipotálamo/química , Rim/química , Fígado/química , Pulmão/química , Masculino , Músculo Esquelético/química , Miocárdio/química , RNA Mensageiro/genética , Ratos , Ratos Long-Evans , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/químicaRESUMO
The purpose of this study was to analyze postoperative pain differences in patients undergoing peripheral arm surgery. Differences between patients' perceived pain who received 2 mg of morphine sulfate added to the standard Bier block solution and the standard Bier block solution without morphine were studied. A quasi-experimental nonequivalent control group design was utilized. Thirty adult subjects (22 men and 8 women) ages 21 to 76 years constituted the convenience sample. Pain scores were measured by a verbal descriptor scale at the following times: upon admission to the postanesthesia care unit, at 30 minutes and 60 minutes after surgery, and at 24 hours postoperatively. A two-tailed Mann-Whitney U test was used to analyze pain scores for the two groups (P < .05). No statistically significant differences were found in postoperative pain between the group receiving a Bier block solution with 2 mg of morphine sulfate and the group with a standard Bier block solution without morphine sulfate. The mean scores for the morphine sulfate group were lower in each time period measured. This study suggests a questionable benefit for adding 2 mg of morphine sulfate to a Bier block solution. A larger sample may have yielded different results. Many issues remain undecided regarding the potential role of opioids in various regional anesthetic techniques. Further studies are warranted to investigate the peripheral effects of opioids and to understand the mechanisms of action of opioid analgesics at peripheral sites.
