Evidence of presynaptic and postsynaptic action of local anesthetics in rats

PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS: LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.

Reduced hippocampal GABAergic function in Wistar audiogenic rats

Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19 percent and its maximum slope by 73 ± 21 percent. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46 percent) or slope (11 ± 29 percent). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.

Specific actions of general anesthetics at molecular and cellular levels

Up to the present, and despite a widespread approach to explain the cellular and molecular basis of general anesthesia, the complex state of narcosis is still not completely understood. The continuing search for the mechanisms of action is prompted both by the clinical importance of these drugs and by the recognition that the work is related to basic studies of the brain, which represents the most important system in man. The observation that pressures of the order of 150 atmospheres restores consciousness to an anesthetized animal has very long been central to theories of the molecular mechanisms underlying general anesthesia. Many workers have argued that, because pressure can only act by reducing volume, anesthetics must be exerting their effects by increasing the volume of the cell membrane. Furthermore, it has been known for decades that anesthetics perturb the phospholipid bilayer of the cell membrane in proportion to their lipid solubility. However, recent neurophysiological, biochemical and pharmacological work has focused on membrane proteins in the single neuron, the smallest functional unit in the central nervous system [CNS]. In this review, the effects of intravenous and inhalational general anesthetics on ion channels and synaptic transmissions potentially relevant to the phenomena of anesthesia are described including the conflict between the classic lipid and the modern protein theories. The review will concentrate especially on the postsynaptic ligandgated ion-channels

Oxido nítrico en la nocicepción / Nitric oxide and nociception

Las investigaciones en el campo del dolor y de la analgesia se están enfocando hacia los eventos celulares y moleculares subyacentes a los mecanismos de dolor crónico. En particular, mucha atención está recibiendo el óxido nítrico (ON), un nuevo tipo de neurotransmisor. El ON es un radical libre gaseoso e inestable que resulta de la oxidación de la L-arginina a L-citrulina en una reacción catalizada por la sintasa del óxido nítrico. El ON cumple un papel de molécula citotóxica de macrófagos activados y de relajante de músculo liso. Además de estas funciones, el ON actúa como neuromodulador y/o neurotransmisor en el sistema nervioso. Reportes recientes han comenzado a definir el papel del ON en los procesos nociceptivos a nivel de la médula espinal. Asociado a receptores sensibles al N-metil-D-aspartato (NMDA), parece estar involucrado en los mecanismos suyacentes de la hiperalgesia térmica, involucrado en la facilitación de reflejos térmicos. Es más, parece que la producción sostenida del On y la subsecuente activación de la guanilato ciclasa soluble en la médula espinal lumbar, son condiciones requeridas para el mantenimiento de la hiperalgesia térmica producida en modelos del dolor persistente. La inhibición de la sintasa del ON con nitro-L-arginina bloquea la tolerancia a la morfina en ratones. La nitro-L-arginina también es capaz de revertir lentamente tolerancia preexistente, además de reducir la dependencia y de revertir la dependencia a la droga previemente establecida. La acción del ON es selectivo para la tolerancia y dependencia a receptores del subtipo µ