RESUMO
Herein, we report detailed studies on a series of o-(silyl)(boryl)benzenes (1-4), in which the two Lewis acid centers consisting of silicon and boron atoms are linked via an o-phenylene skeleton. o-(Fluorosilyl)(dimesitylboryl)benzenes 1 and 2 were prepared by the reaction of fluorodimesitylborane with [o-(fluorodimethylsilyl)phenyl]lithium (7) and [o-(fluorodiphenylsilyl)phenyl]lithium (8), respectively. o-(Difluorosilyl)(dimesitylboryl)benzenes 3 and 4 were also prepared by the reaction of fluorodimesitylborane with o-{[di(methoxy)methylsilyl]phenyl}lithium (11) and o-{[di(methoxy)phenylsilyl]phenyl}lithium (12), respectively, and their subsequent treatment with HF·pyridine. Compounds 1-4 readily capture a fluoride ion in the presence of 18-crown-6 or [2.2.2]cryptand to afford their corresponding µ-fluoro-bridged ate complexes (15-18). The structures of 15-18 were revealed by NMR spectroscopy and X-ray crystallography. DFT studies and natural bond orbital analysis of 15-18 were conducted to elucidate the nature of the Si-F and B-F bonding interactions in the µ-fluoro-bridges. The fluoride ion affinities of 1-4 were investigated by 1H NMR spectroscopy to monitor their competitive reactions. The dynamic behaviors of 15-18 at variable temperatures were monitored using 19F NMR spectroscopy.
RESUMO
To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86-88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury.
Assuntos
N-Metilaspartato/metabolismo , Dor/fisiopatologia , Células do Corno Posterior/fisiologia , Receptores de N-Metil-D-Aspartato/deficiência , Animais , Sítios de Ligação , Dependovirus/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Formaldeído , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Hiperalgesia/induzido quimicamente , Hiperalgesia/complicações , Hiperalgesia/fisiopatologia , Técnicas In Vitro , Integrases/administração & dosagem , Integrases/genética , Integrases/metabolismo , Íntrons , Região Lombossacral , Masculino , Camundongos , Camundongos Mutantes , Atividade Motora/genética , Dor/induzido quimicamente , Dor/complicações , Medição da Dor , Técnicas de Patch-Clamp , Células do Corno Posterior/citologia , Células do Corno Posterior/metabolismo , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/genética , Transdução Genética , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
1. We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. 2. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol microl(-1) h(-1)) or saline (IT-S: 1 microl h(-1)) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg(-1)) or saline (IP-S: 3 ml kg(-1)) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. 3. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine + IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine + i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. 4. For the IT-M + IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. 5. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. 6. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. 7. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance.
